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724. 




The Social and 
Ethical Issues or 
Genetic Engineering 
with Human Beings 




President's Commission for the Study of 
Ethical Problems in Medicine and 
Biomedical and Behavioral Research 



Library of Congress card number 83-600500 

For sale by the Superintendent of Documents 

U.S. Government Printing Office 

Washington, D.C. 20402 



Splicing 
life 



A Report on the Social 
and Ethical Issues of 
Genetic Engineering 
with Human Beings 



November 1982 



President's Commission for the Study of 
Ethical Problems in Medicine and 
Biomedical and Behavioral Research 



President's Commission for the Study of Ethical 
Problems in Medicine and Biomedical and 
Behavioral Research 

Morris B. Abram, M.A., J.D., LL.D., Chairman, 
New York, N.Y. 



H. Thomas Ballantine, M.D., 
M.S., D.Sc. 

Harvard Medical School 

George R. Dunlop, M.D. 
University of Massachusetts 

Bruce K. Jacobson, M.D. 
Southwestern Medical School 

John J. Moran, B.S. 
Houston, Texas 

Arno G. Motulsky, M.D. 
University of Washington 



DaherB. Rahi, D.O. 

St. Clair Shores, Michigan 

Seymour Siegel, D.H.L. 
Jewish Theological 
Seminary of America, 
New York 

Lynda Smith, B.S. 
Colorado Springs, Colorado 

Kay Toma, M.D. 
Bell, California 

Charles J. Walker, M.D. 
Nashville, Tennessee 



Staff 



Alexander M. Capron, LL.B., Executive Director 



Deputy Director 

Barbara Mishkin, M.A., J.D. 

Assistant Directors 
Joanne Lynn, M.D., M.A. 
Alan Meisel, J.D. 

Professional Staff 
Mary Ann Baily, Ph.D. 
Allen Buchanan, Ph.D. 
Andrew Burness, M.B.A. 
Kathryn Kelly, M.S.W. 
Susan Morgan 
Marian Osterweis, Ph.D. 
Renie Schapiro, M.P.H. 

Research Assistants 
Michelle Leguay 
Katherine Locke 
Jeffrey Stryker 

Consultants 
Bradford H. Gray, Ph.D. 
Tabitha M. Powledge, M.S. 
Dorothy Vawter 



Administrative Officer 
Anne Wilburn 

Editor 
Linda Starke 

Support Staff 
Florence Chertok 
Gretchen Erhardt 
Ruth Morris 
Clara Pittman 
Kevin Powers 
Nancy Watson 

President's Commission 
Commonwealth Fellows and 
Student Interns 
Susan Formaker (1982) 
Jeffrey Katz (1981) 
Kenneth Kim (1982) 
Eddie Lockard (1982) 
Stephen Massey (1982) 
Lisa Rovin (1982) 
Mindy Werner (1982) 




Suite 555, 2000 K Street, N.W., Washington, DC 20006 (202) 653-8051 

November 16, 1982 



President's Commission for the Study of Ethical Problems 
in Medicine and Biomedical and Behavioral Research 



The President 
The White House 
Washington, D.C. 20500 

Dear Mr. President: 

On behalf of the President's Commission for the Study of 
Ethical Problems in Medicine and Biomedical and Behavioral 
Research, I am pleased to transmit Splicing Life , our Report 
on the social and ethical issues of genetic engineering with 
human beings. This study, which was not within the Commission's 
legislative mandate, was prompted by a letter to your predecessor 
in July 1980 from Jewish, Catholic, and Protestant church 
associations. We embarked upon it, pursuant to § 1802(a) (2) 
of our statute, at the urging of the President's Science 
Advisor. 

Some people have suggested that developing the capability 
to splice human genes opens a Pandora's box, releasing mischief 
and harm far greater than the benefits for biomedical science. 
The Commission has not found this to be the case. The laboratory 
risks in this field have received careful attention from the 
scientific community and governmental bodies. The therapeutic 
applications now being planned are analogous to other forms 
of novel therapy and can be judged by general ethical standards 
and procedures , informed by an awareness of the particular 
risks and benefits that accompany each attempt at gene splicing. 

Other, still hypothetical uses of gene splicing in human 
beings hold the potential for great benefit, such as heretofore 
impossible forms of treatment, as well as raising fundamental 
new ethical concerns. The Commission believes that it would 
be wise to have engaged in careful prior thought about steps 
such as treatments that can lead to heritable changes in 
human beings or those intended to enhance human abilities 
rather than simply correct deficiencies caused by well-defined 
genetic disorders. In light of a detailed analysis of the 
ethical and social issues of this subject — issues beyond 
the purview of existing mechanisms for Federal oversight — the 
Commission suggests several possible means, in the private 
as well as the public sector, through which these important 
matters can receive the necessary advance consideration. 

The Commission is pleased to have had an opportunity to 
participate in the consideration of this issue of public 
concern and importance. 




Morris B. Abram 
Chairman 




President's Commission for the Study of Ethical Problems 
in Medicine and Biomedical and Behavioral Research 
Suite 555, 2000 K Street, N.W., Washington, DC 20006 (202) 653-8051 



November 16, 1982 



The Honorable George Bush 
President 

United States Senate 
Washington, D.C. 20510 

Dear Mr. President: 

On behalf of the President's Commission for the Study of 
Ethical Problems in Medicine and Biomedical and Behavioral 
Research, I am pleased to transmit Splicing Life , our Report 
on the social and ethical issues of genetic engineering with 
human beings. This study, which was not within the Commission's 
legislative mandate, was prompted by a letter to the President 
in July 1980 from Jewish, Catholic, and Protestant church 
associations. We embarked upon it, pursuant to § 1802(a) (2) 
of our statute, at the urging of the President's Science 
Advisor. 

Some people have suggested that developing the capability 
to splice human genes opens a Pandora's box, releasing mischief 
and harm far greater than the benefits for biomedical science. 
The Commission has not found this to be the case. The laboratory 
risks in this field have received careful attention from the 
scientific community and governmental bodies. The therapeutic 
applications now being planned are analogous to other forms 
of novel therapy and can be judged by general ethical standards 
and procedures, informed by an awareness of the particular 
risks and benefits that accompany each attempt at gene splicing. 

Other, still hypothetical uses of gene splicing in human 
beings hold the potential for great benefit, such as heretofore 
impossible forms of treatment, as well as raising fundamental 
new ethical concerns. The Commission believes that it would 
be wise to have engaged in careful prior thought about steps 
such as treatments that can lead to heritable changes in 
human beings or those intended to enhance human abilities 
rather than simply correct deficiencies caused by well-defined 
genetic disorders. In light of a detailed analysis of the 
ethical and social issues of this subject — issues beyond 
the purview of existing mechanisms for Federal oversight — the 
Commission suggests several possible means, in the private 
as well as the public sector, through which these important 
matters can receive the necessary advance consideration. 

The Commission is pleased to have had an opportunity to 
participate in the consideration of this issue of public 
concern and importance. 



Respectfully, 




Morris B. Abram 
Chairman 



President's Commission for the Study of Ethical Problems 
in Medicine and Biomedical and Behavioral Research 
Suite 555, 2000 K Street, N.W., Washington, DC 20006 (202) 653-8051 

November 16, 1982 

The Honorable Thomas P. O'Neill, Jr. 
Speaker 

United States House of Representatives 
Washington, D.C. 20515 

Dear Mr. Speaker: 

On behalf of the President's Commission for the Study of 
Ethical Problems in Medicine and Biomedical and Behavioral 
Research, I am pleased to transmit Splicing Life , our Report 
on the social and ethical issues of genetic engineering with 
human beings. This study, which was not within the Commission's 
legislative mandate, was prompted by a letter to the President 
in July 1980 from Jewish, Catholic, and Protestant church 
associations. We embarked upon it, pursuant to § 1802(a) (2) 
of our statute, at the urging of the President's Science 
Advisor. 

Some people have suggested that developing the capability 
to splice human genes opens a Pandora's box, releasing mischief 
and harm far greater than the benefits for biomedical science. 
The Commission has not found this to be the case. The laboratory 
risks in this field have received careful attention from the 
scientific community and governmental bodies. The therapeutic 
applications now being planned are analogous to other forms 
of novel therapy and can be judged by general ethical standards 
and procedures, informed by an awareness of the particular 
risks and benefits that accompany each attempt at gene splicing. 

Other, still hypothetical uses of gene splicing in human 
beings hold the potential for great benefit, such as heretofore 
impossible forms of treatment, as well as raising fundamental 
new ethical concerns. The Commission believes that it would 
be wise to have engaged in careful prior thought about steps 
such as treatments that can lead to heritable changes in 
human beings or those intended to enhance human abilities 
rather than simply correct deficiencies caused by well-defined 
genetic disorders. In light of a detailed analysis of the 
ethical and social issues of this subject — issues beyond 
the purview of existing mechanisms for Federal oversight — the 
Commission suggests several possible means, in the private 
as well as the public sector, through which these important 
matters can receive the necessary advance consideration. 

The Commission is pleased to have had an opportunity to 
participate in the consideration of this issue of public 
concern and importance. 

Res pect fully, 

Morris B. Abram 
Chairman 




Table of Contents 



Summary of Conclusions and Recommendations 1 

Chapter 1: Clarifying the Issues 7 

The Meaning of the Term "Genetic Engineering" 8 

Changes in the Genetic Landscape 8 

Manipulating Genes 8 

Concerns About Genetic Engineering 10 

Scientific Self-Regulation 10 

Governmental Supervision 11 

Deeper Anxieties 13 

The Commission's Study 18 

Objectives 18 

Educating the public 20 

Clarifying concerns expressed in slogans 21 

Identifying the public policy issues 22 

Evaluating the need for oversight 23 

The Process of Study 23 

Chapter 2: The Dawn of a New Scientific Era 25 

Discovering Life's Mysteries 25 

Cells and Genes 26 

Accidents and Diseases 28 

The Technology of Gene Splicing 30 

Recombinant DNA Techniques 30 

Cell Fusion 35 

Genetically Engineered Medical Products 36 

Production of Drugs and Biologies 36 

Cancer Diagnosis and Therapy 38 

Genetic Screening and Diagnosis 38 

Curing Genetic Disorders 42 

Somatic Cells 42 

Germ-Line Cells 45 

Genes or Genies? 48 

Chapter 3: Social and Ethical Issues 51 

Concerns About "Playing God" 53 

Religious Viewpoints 53 

Fully Understanding the Machinery of Life 54 

Arrogant Interference with Nature 55 

Creating New Life Forms 56 



Concerns About Consequences 60 

What Are the Likely Outcomes? 60 

Medical applications 60 

Evolutionary impact on human beings 62 

Will Benefit or Harm Occur? 64 

Parental rights and responsibilities 64 

Societal obligations 66 

The commitment to equality of opportunity 67 
Genetic malleability and the sense of personal 

identity 68 

Changing the meaning of being human 68 

Unacceptable uses of gene splicing 71 
Distributing the power to control gene splicing 73 

Commercial-academic relations 74 

Continuing Concerns 77 

Chapter 4: Protecting the Future 81 

Objectives 82 

Revising RAC 84 

Appendix A: Glossary 89 

Appendix B: Letter from Three General Secretaries 95 

Appendix C: Federal Government Involvement in 

Genetic Engineering 97 

Appendix D: The Commission's Process 107 

Index 113 



Figures 

Figure 1. Cell Structure 27 
Figure 2. Replication of DNA 28 
Figure 3. Transduction: The Transfer of Genetic 

Material in Bacteria by Means of 

Viruses 31 
Figure 4. Conjugation: The Transfer of Genetic 

Material in Bacteria by Mating 32 
Figure 5. Creation of "Sticky Ends" by a 

Restriction Enzyme 33 
Figure 6. Splicing Human Genes into Plasmid 34 



Summary of 
Conclusions and 
Recommendations 



This Report addresses some of the major ethical and social 
implications of biologists' newly gained ability to manipulate — 
indeed, literally to splice together — the material that is respon- 
sible for the different forms of life on earth. The Commission 
began this study because of an urgent concern expressed to the 
President that no governmental body was "exercising adequate 
oversight or control, nor addressing the fundamental ethical 
questions" of these techniques, known collectively as "genetic 
engineering," particularly as they might be applied directly to 
human beings. 1 

When it first examined the question of governmental 
activity in this area, in the summer of 1980, the Commission 
found that this concern was well founded. Not only was no 
single agency charged with exploring this field but a number of 
the agencies that would have been expected to be involved 
with aspects of the subject were unprepared to deal with it, 
and the Federal interagency body set up to coordinate the field 
was not offering any continuing leadership. Two years later, 
possibly because of the Commission's attention, it appears the 
Federal agencies are more aware of, and are beginning to deal 
with, questions arising from genetic engineering, although their 
efforts primarily address the agricultural, industrial, and 
pharmaceutical uses of gene splicing rather than its diagnostic 
and therapeutic uses in human beings. 2 

The Commission did not restrict its examination of the 
subject to the responses of Federal agencies, however, because 
it perceived more important issues of substance behind the 
expressed concern about the lack of Federal oversight. The 
Commission chose, therefore, to address these underlying 



1 See Appendix B, pp. 95-96 infra. 

2 See Appendix C, pp. 97-106 infra. 



2 



Splicing Life 



issues, although certainly not to dispose of them. On many 
points, the Commission sees its contribution as stimulating 
thoughtful, long-term discussion rather than truncating such 
thinking with premature conclusions. 

This study, undertaken within the time limitations im- 
posed by the Commission's authorizing statute, is seen by the 
Commission as a first step in what ought to be a continuing 
public examination of the emerging questions posed by devel- 
opments and prospects in the human applications of molecular 
genetics. First, the report attempts to clarify concerns about 
genetic engineering and to provide technical background 
intended to increase public understanding of the capabilities 
and potential of the technique. Next, it evaluates the issues of 
concern in ways meaningful for public policy, and analyses the 
need for an oversight mechanism. 

To summarize, in this initial study the Commission finds 

that: 

(1) Although public concern about gene splicing arose in 
the context of laboratory research with microorganisms, it 
seemed to reflect a deeper anxiety that work in this field might 
remake human beings, like Dr. Frankenstein's monster. These 
concerns seem to the Commission to be exaggerated. It is true 
that genetic engineering techniques are not only a powerful 
new tool for manipulating nature — including means of curing 
human illness — but also a challenge to some deeply held 
feelings about the meaning of being human and of family 
lineage. But as a product of human investigation and ingenuity, 
the new knowledge is a celebration of human creativity, and 
the new powers are a reminder of human obligations to act 
responsibly. 

(2) Genetic engineering techniques are advancing very 
rapidly. Two breakthroughs in animal experiments during 1981 
and 1982, for example, bring human applications of gene 
splicing closer: in one, genetic defects have been corrected in 
fruit flies; in another, artificially inserted genes have func- 
tioned in succeeding generations of mammals. 

(3) Genetic engineering techniques are already demon- 
strating their great potential value for human well-being. The 
aid that these new developments may provide in the relief of 
human suffering is an ethical reason for encouraging them. 

• Although the initial benefits to human health involve 
pharmaceutical applications of the techniques, direct 
diagnostic and therapeutic uses are being tested and 
some are already in use. Those called upon to review 
such research with human subjects, such as local 
Institutional Review Boards, should be assured of 
access to expert advice on any special risks or 
uncertainties presented by particular types of genetic 
engineering. 



Summary 



3 



• Use of the new techniques in genetic screening will 
magnify the ethical considerations already seen in 
that field because they will allow a larger number of 
diseases to be detected before clinical symptoms are 
manifest and because the ability to identify a much 
wider range of genetic traits and conditions will 
greatly enlarge the demand for, and even the objec- 
tives of, prenatal diagnosis. 

(4) Many human uses of genetic engineering resemble 
accepted forms of diagnosis and treatment employing other 
techniques. The novelty of gene splicing ought not to erect any 
automatic impediment to its use but rather should provoke 
thoughtful analysis. 

• Especially close scrutiny is appropriate for any proce- 
dures that would create inheritable genetic changes; 
such interventions differ from prior medical interven- 
tions that have not altered the genes passed on to 
patients' offspring. 

• Interventions aimed at enhancing "normal" people, as 
opposed to remedying recognized genetic defects, are 
also problematic, especially since distinguishing 
"medical treatment" from "nonmedical enhancement" 
is a very subjective matter; the difficulty of drawing a 
line suggests the danger of drifting toward attempts to 
"perfect" human beings once the door of "enhance- 
ment" is opened. 

(5) Questions about the propriety of gene splicing are 
sometimes phrased as objections to people "playing God." The 
Commission is not persuaded that the scientific procedures in 
question are inherently inappropriate for human use. It does 
believe, nevertheless, that objections of this sort, which are 
strongly felt by many people, deserve serious attention and 
that they serve as a valuable reminder that great powers imply 
great responsibility. If beneficial rather than catastrophic 
consequences are to flow from the use of "God-like" powers, 
an unusual degree of care will be needed with novel applica- 
tions. 

(6) The generally very reassuring results of laboratory 
safety measures have led to a relaxation of the rules governing 
gene splicing research that were established when there was 
widespread concern about the potential risks of the research. 
The lack of definitive proof of danger or its absence has meant 
that the outcome — whether to restrict certain research — has 
turned on which side is assigned the burden of proving its case. 
Today those regulating gene splicing research operate from the 
assumption that most such research is safe, when conducted 
according to normal scientific standards; those opposing that 
position face the task of proving otherwise. 



4 



Splicing Life 



• The safety issue will arise in a wider context as gene 
splicing is employed in manufacturing, in agriculture 
and other activities in the general environment, and in 
medical treatment. As a matter of prudence, such 
initial steps should be accompanied by renewed 
attention to the issue of risk (and by continued 
research on that subject). 

• Efforts to educate the newly exposed population to 
the appropriate precautions, whenever required, and 
serious efforts to monitor the new settings (since 
greater exposure increases the opportunity to detect 
low-frequency events) should be encouraged. In gen- 
eral, the questions of safety concerning gene splicing 
should not be viewed any differently than comparable 
issues presented by other scientific and commercial 
activities. 

(7) The Recombinant DNA Advisory Committee (RAC) at 
the National Institutes of Health has been the lead Federal 
agency in genetic engineering. Its guidelines for laboratory 
research have evolved over the past seven years in response to 
changes in scientific attitudes and knowledge about the risks 
of different types of genetic engineering. The time has now 
come to broaden the area under scrutiny to include issues 
raised by the intended uses of the technique rather than solely 
the unintended exposure from laboratory experiments. 

• It would also be desirable for this "next generation" 
RAC to be independent of Federal funding bodies 
such as NIH, which is the major Federal sponsor of 
gene splicing research, to avoid any real or perceived 
conflict of interest. 

(8) The process of scrutiny should involve a range of 
participants with different backgrounds — not only the 
Congress and Executive Branch agencies but also scientific 
and academic associations, industrial and commercial groups, 
ethicists, lawyers, religious and educational leaders, and 
members of the general public. 

• Several formats deserve consideration, including ini- 
tial reliance on voluntary bodies of mixed public- 
private membership. Alternatively, the task could be 
assigned to this Commission's successor, as one 
among a variety of issues in medicine and research 
before such a body, or to a commission concerned 
solely with gene splicing. 

• Whatever format is chosen, the group should be 
broadly based and not dominated by geneticists or 
other scientists, although it should be able to turn to 
experts to advise it on the laboratory, agricultural, 
environmental, industrial, pharmaceutical, and human 
uses of the technology as well as on international 



Summary 



5 



scientific and legal controls. Means for direct liaison 
with the government departments and agencies in- 
volved in this field will also be needed. 

(9) The need for an appropriate oversight body is based 
upon the profound nature of the implications of gene splicing 
as applied to human beings, not upon any immediate threat of 
harm. Just as it is necessary to run risks and to accept change 
in order to reap the benefits of scientific progress, it is also 
desirable that society have means of providing its "informed 
consent," based upon reasonable assurances that risks have 
been minimized and that changes will occur within an accept- 
able range. 



Clarifying 
the Issues 



Human beings continually pursue greater knowledge 
about themselves and their world. Science provides a powerful 
key in that quest, unlocking many mysteries. But even as 
science answers questions, it generates many new ones; new 
knowledge creates new challenges. The recently acquired 
capability to manipulate the genetic material of all living things 
is an important — even revolutionary — advance in the trajecto- 
ry of human knowledge. But, like revolutionary insights of the 
past that enriched understanding, it also unsettles notions that 
once seemed fixed and comfortable. This Report attempts to 
contribute to the public discussion of the social and ethical 
implications of genetic engineering by clarifying some of the 
issues raised by the new technology and initiating an examina- 
tion of possible procedural mechanisms for responding to 
them. 

The Commission undertook this study in response to a 
request addressed to the President on June 20, 1980, by the 
General Secretaries of the National Council of Churches, the 
Synagogue Council of America, and the United States Catholic 
Conference. In the wake of the Supreme Court decision that 
allowed the patenting of new forms of life, the religious 
organizations warned that 

We are rapidly moving into a new era of fundamental 
danger triggered by the rapid growth of genetic engineer- 
ing. Albeit, there may be opportunity for doing good; the 
very term suggests the danger. 1 
Describing the questions as "moral, ethical, and religious, 
[dealing] with the fundamental nature of human life and the 
dignity and worth of the individual human being," the three 



1 For the full text of the letter from the religious bodies, see Appendix 
B, pp. 95-96 infra. 



8 



Splicing Life: Chapter 1 



religious representatives called upon President Carter to 
remedy the lack of "adequate oversight or control" among 
governmental bodies by providing "a way for representatives 
of a broad spectrum of our society to consider these matters 
and advise the government on its necessary role." In response 
to a request from the President's Science Advisor, the Commis- 
sion decided in September 1980 to study the ethical and social 
implications of this new area of biotechnology as it applies to 
human beings. 

The Meaning of the Term "Genetic Engineering" 

Changes in the Genetic Landscape. For at least 10,000 
years — since long before the principles of classical genetics 2 
had been scientifically established — human beings have 
brought about deliberate genetic changes in plants and animals 
through traditional reproductive methods. Many of the domes- 
tic animals, crops, and ornamental plants in existence today 
are human creations, achieved through selective breeding 
aimed at enhancing desired characteristics. In a broad sense, 
such genetic manipulation by breeding for a desired outcome 
might be considered genetic "engineering." 

In addition to these intended changes, many alterations 
have occurred inadvertently through other practices, including 
the ordinary practice of medicine. Many people with genetic 
disorders who in the past would have died without any 
natural-born children now live into adulthood, passing on 
genes for the disorder. The use of exogenous insulin to treat 
diabetes and the prescription of eyeglasses for myopia are two 
examples of interventions that increase the prevalence in the 
population of certain genes that can have deleterious effects 
for individuals. Medical screening for genetic disorders and 
carrier status, when followed by decisions by the individuals 
screened to alter reproductive behavior, also affects the 
occurrence of genes in the population. 3 These changes have 
been a by-product of medical and technological interventions 
aimed at individuals, not at the general population. 

Manipulating Genes. In 1965 the term "genetic engineer- 
ing" was coined for what has come to be a wide range of 
techniques by which scientists can add genetically determined 
characteristics to cells that would not otherwise have pos- 
sessed them. 4 Compared with traditional means of altering the 



2 For definitions of the technical terms used throughout this Report, 
see Glossary, Appendix A, pp. 89-93 infra. 

3 A discussion of genetic screening can be found in the Commission's 
report, Screening and Counseling for Genetic Conditions, U.S. 
Government Printing Office, Washington (1983). 

4 Rollin D. Hotchkiss, Portents for a Genetic Engineering, 56 J. 
Heredity 197 '1965). 



Clarifying the Issues 



9 



gene pool, the ability to alter genetic material directly offers 
specificity and, in the case of changes in germ cells, speed. 

The rapidity with which this field has developed is 
startling. Scientists' understanding of the structure of deoxyri- 
bonucleic acid (DNA), which is common to almost all living 
cells, and their discovery of its remarkable capacity for 
encoding and passing on genetic characteristics are post-1953 
developments. In the early 1970s, scientists learned how to 
isolate specific DNA sequences from one species and attach 
this genetic material — "recombinant DNA" — to a different 
species. Rapid progress has also been made with cell fusion, 
another means of genetic engineering that permits the contents 
of two cells from different organisms to be merged in such a 
way that the hybrid cell continues to function and reproduce. 

The layperson's term "gene splicing" describes the tech- 
nology well, for like a seaman putting two pieces of rope 
together, a scientist using the recombinant DNA method can 
chemically "snip" a DNA chain at a predetermined place and 
attach another piece of DNA at that site. In cell fusion, it is two 
entire cells that are "spliced" together. Chapter Two provides a 
fuller discussion of gene splicing and its applications. 

The term genetic engineering has sometimes been used to 
refer to several other new technologies such as in vitro 
fertilization 5 and cloning 6 of an organism. These techniques do 



5 In vitro fertilization (IVF) is a technique for achieving fertilization of 
an egg outside of the body, in a laboratory dish (from the Latin, in 
vitro, for "in glass"). In its therapeutic uses it also encompasses 
embryo transfer to a uterus. One or more eggs are surgically removed 
from an ovary of a woman with obstructed Fallopian tubes, fertilized 
with her husband's sperm in a laboratory dish, allowed to develop 
there for a few days, and then transferred into the woman's uterus, 
where the pregnancy proceeds. IVF has received a great deal of 
publicity in the past few years as some previously infertile women 
have given birth following the use of this technique. The Commission 
decided in May 1980 not to take up the subject of human in vitro 
fertilization because the Ethics Advisory Board of the Department of 
Health and Human Services had studied the subject at length. Action 
has not yet been taken on the EAB's May 4, 1979, report and 
recommendations to the Secretary. 

6 Cloning, the production of genetically identical copies, can apply to 
cells or whole organisms. Although the idea of creating clones in the 
laboratory is new, many species of plant and animals, including 
humans, produce natural clones. For example, identical twins, triplets, 
etc., are members of a clone, since they are derived from the same 
fertilized egg. 

In 1981 researchers produced a clone of mice from embryonic 
cells. Nuclei taken from a seven-day-old embryo were inserted into 
newly fertilized mouse eggs from which the nuclei had been removed. 
Jean L. Marx, Three Mice "Cloned" in Switzerland, 211 Science 375 
(1981]. These eggs were then implanted into the uterus of "foster 



10 



Splicing Life: Chapter 1 



not necessarily involve genetic manipulation, although they 
might be used in conjunction with such manipulation in 
particular situations. They are regarded here as examples of 
reproductive (rather than genetic) technologies and thus are 
outside the scope of this Report. 

Concerns About Genetic Engineering 

Genes are perhaps the most tangible correlates of who a 
person is as an individual and as a member of a family, race, 
and species. They are people's fixed legacy to their descen- 
dants. Genetic information can alter an individual's most 
personal decisions about reproduction. It is not surprising, 
therefore, that genetics is peculiarly prone to controversy. 

Scientific Self-Regulation. Although issues in genetics 
arouse wide public interest, the initial concern about genetic 
engineering did not come from the public but from scientists 
actually involved in the research. Genetic material is essential- 
ly the same in most living things, and therefore in theory gene 
transfers can be carried out between any two organisms. In the 
early 1970s, fears that exploiting this interchangeability could 
cause the uncontrollable spread of serious disease or damage 
the environment led some of the first scientists working with 
gene splicing techniques to raise questions about the unpredict- 
able consequences of their work. For example, one of the early 
planned experiments involved attempts to splice SV40, a virus 
known to cause cancer in mice and hamsters, into a bacterium. 
What, scientists wondered, would happen if that experimental 
bacterium was released outside the laboratory and began 
making billions of copies of itself — and its new cancer-causing 
gene? The worries were compounded by the fact that the 
experimental bacterium was closely related to one normally 
found in human beings. Was it possible that the laboratory 
bacterium, carrying a cancer virus, might be infectious in 
humans or cause a cancer epidemic? 



mothers" who subsequently gave birth to genetically identical mice. 
The success demonstrated that the embryonic cells retain their 
totipotency (that is, their ability to develop into a complete mouse). 
Developing a clone from an existing individual, rather than embryonic 
cells, is more difficult since these cells have already differentiated and 
would need to regain totipotency. 

In light of the public attention cloning has received, it is important 
to emphasize that even if a cell from a developed organism could 
produce a clone, it would not result in an instantaneous "carbon 
copy" of the original. In cloning, the genetic material is inserted into a 
recently fertilized egg to produce a new generation with the same 
genetic makeup. The technology to clone a human does not — and may 
never — exist. Moreover, the critical nongenetic influences on develop- 
ment make it difficult to imagine producing a human clone who would 
act or appear "identical." 



Clarifying the Issues 



11 



Such concerns led in the fall of 1973 and summer of 1974 to 
the publication, in both Science and Nature, of letters signed 
by several leading molecular biologists on behalf of those most 
centrally involved in the field. 7 The first letter called attention 
to the issues and asked the National Academy of Science to 
establish a committee, and the second urged scientists to hold 
off on certain recombinant DNA experiments until the risks 
could be assessed. This process of assessment was pushed 
forward by the new NAS committee, chaired by Paul Berg of 
Stanford University, which organized a meeting in February 
1975 at the Asilomar conference center in California. At the 
meeting were 150 molecular biologists, microbiologists, plant 
physiologists, industrial researchers, and other scientists from 
both the United States and abroad, four American lawyers, 
and a large group of journalists as observers. The Asilomar 
participants proposed that the self-imposed moratorium be 
lifted for most recombinant DNA research, subject to specified 
physical and biological containment measures that would be 
graduated according to the risk of the experiment. 8 

Governmental Supervision. After the meeting, the Director 
of the National Institutes of Health (NIH) asked the Recombi- 



7 Maxine Singer and Dieter Soil, Guidelines for DNA hybrid molecules 
(Letter), 181 Science 1114 (1973); Paul Berg et ah, Potential biohazards 
of recombinant DNA molecules (Letter), 185 Science 303 (1974). 
Taking as his starting point the recombinant DNA experience, a 
leading ethicist has argued for an expanded vision of scientific 
responsibility: 

If the essence of good scientific research is to leave no stone 
unturned, it is no less pertinent to moral thought. A scientific 
researcher would, in strictly scientific terms, be considered 
poor if he did not allow his mind to roam in all directions during 
the phase of hypothesis development, taking seriously any idea 
that might produce a promising lead.... The same is true of 
moral thinking, particularly when it bears on the future 
consequences of our actions. We are obliged to explore all 
possibilities, however vague and remote; and the moral person 
will also end by throwing most of them out — most, finally, but 
not all. Since we surely now know that scientific research, 
whether basic or applied, is a source of enormous power for 
both good and ill, the scientific researcher has, then, an 
obligation to be as active in his moral imagination as in his 
scientific imagination. We ask the same of any person in a 
position of power. 
Daniel Callahan, Ethical Responsibility in Science in the Face of 
Uncertain Consequences, 265 Ann. N.Y. Acad. Sci. 1,6 (1976). 

8 Michael Rogers, Biohazard, Alfred A. Knopf, New York (1973) at 51- 
101; William Bennett and Joel Gurin, Science that Frightens Scientists, 
The Atlantic 43, 49-50 (Feb. 1977); Roger B. Dworkin, Science, 
Society, and the Expert Town Meeting: Some Comments on Asilomar, 
51 S. Cal. L. Rev. 1471 (1978). 



12 



Splicing Life: Chapter 1 



nant DNA Advisory Committee (RAC) that had been estab- 
lished the previous October to consider the Asilomar report 
and make recommendations. RAC issued guidelines in June 
1976 (under the auspices of NIH) for the conduct of recombi- 
nant DNA experiments. 9 The guidelines are binding on re- 
searchers receiving Federal funds, and — the Commission was 
informed during this study — the private sector has complied 
with them voluntarily. 

Concern about "biohazards" also found its way to Capitol 
Hill. Several bills were introduced in the mid-1970s to regulate 
gene splicing research, although none passed. 10 The political 
rhetoric of proponents and opponents escalated as the debates 
moved to the community level; in Cambridge, Massachusetts, 
and some other localities with major research institutions, 
concerns about the safety of recombinant DNA experiments 
aroused loud and often vitriolic public debates. 11 Several 
communities enacted ordinances restricting gene splicing re- 
search. 12 

Meanwhile, RAC became a "second generation" body in 
which scientific members were joined by a larger representa- 
tion of public members. As a 25-member body that now meets 
three to four times a year, it continues to oversee implementa- 
tion of the NIH guidelines. Those restrictions have been 
progressively relaxed as scientists have gained experience 
with the new technology; for most types of experiments, the 



9 41 Federal Register 27902 (July 7, 1976). 

10 In total, 16 bills related to recombinant DNA research were 
introduced in the 95th Congress, in addition to numerous proposed 
bills that were considered but never formally introduced. For a listing 
of the bills see National Institutes of Health, Recombinant DNA 
Research Volume 2, Documents Relating to "NIH Guidelines for 
Research Involving Recombinant DNA Molecules" June 1976- 
November 1977, U.S. Dept. of Health, Education and Welfare, Wash- 
ington (1978). 

11 Nicholas Wade, The Ultimate Experiment, Walker and Company, 
New York (1977) at 127-41. 

12 The Cambridge statute incorporated by reference the RAC guide- 
lines (applying them to industry as well as universities) and estab- 
lished a Cambridge Biohazards Committee for oversight. Between 
1977 and 1979 New York and Maryland and five towns, from New 
Jersey to California, followed the Cambridge model; in 1981 and 1982 a 
second wave of legislation was enacted in several communities in the 
Boston area addressed specifically to the commercial uses of recombi- 
nant DNA technology. Sheldon Krimsky, Local Monitoring of Biotech- 
nology: The Second Wove of Recombinant DNA Laws, 5 Recombinant 
DNA Technical Bull. 79 (1982). See also Cambridge, Mass. Ordinance 
955, Ordinance for the Use of Recombinant DNA Technology in the 
City of Cambridge (April 2, 1981); Waltham, Mass. General Ordi- 
nances ch. 22 (1981); Michael D. Stein, Boston Strikes Out: Local DNA 
Guidelines, 292 Nature 283 (1981). 



Clarifying the Issues 



13 



opponents now bear the burden of proving danger, rather than 
the proponents having to prove safety. 13 

No physical injuries have been found to have resulted 
from new organisms created with gene splicing techniques. 
Most molecular biologists now say they believe that the 
original worries were exaggerated. Nevertheless, a few scien- 
tists continue to maintain that some questions remain unan- 
swered and that continued caution is desirable. This conserva- 
tive approach influenced RAC enough that the committee 
decided in early 1982 not to convert the guidelines into a 
voluntary code of good laboratory practice. Some RAC mem- 
bers also worried that the Federal withdrawal from the field 
would lead states and localities to adopt varying, and often 
more onerous, regulations. 14 

Deeper Anxieties. While the political, public, and scientific 
debate has focused on the hazards of pathogenic organisms, it 
has become apparent that the implications of gene splicing are 
more far-reaching. The consequences of mistakes or failures in 
the laboratory have received attention, but success in learning 
how to manipulate genes could have enormous societal 
consequences as well. The fact that in the mid-1970s laboratory 
experiments with recombinant DNA were assumed for a time 
to be quite risky ought not to mean that forever thereafter any 
research in gene splicing has to overcome a presumption of 
danger. 15 Nevertheless, new knowledge does carry a responsi- 
bility — often weighty — for its application, and the implications 



13 To suggest that the "burden of proof issue lies at the heart of 
the recombinant DNA debate is not to suggest that it is a single 
issue or, indeed, that one determination of who bears what 
burden of going forward with what evidence and persuading 
whom will be satisfactory for all aspects of public policy 
regarding recombinant DNA. One ground for suggesting differ- 
ent burdens might be that the risks motivating concern in the 
first place are of different sorts [i.e., physical versus social 
risks]. Another way of slicing the conceptual pie is according to 
the stage of the research process, between the risks of 
means. . .and the risks of ends. 

A.M. Capron, Prologue: Why Recombinant DNA?, 51 S. Cal. L. Rev. 

973, 977 (1978). 

14 Marjorie Sun, Committee Votes to Keep DNA Rules Mandatory, 215 

Science 949 (1982). 

15 It is generally true that scientific researchers need not 
demonstrate the safety of their investigations as a condition of 
proceeding. But can review be triggered by the expression of 
genuine concern about risks by knowledgeable parties? In the 
case of recombinant DNA, do the initial warnings by scientists 
of possible disasters from research mishaps have continuing 
force once the same scientists suggest that subsequent experi- 
ence has led them to doubt that any unusual risk exists? In 
other words, once triggered can a process of decision be called 



14 



Splicing Life: Chapter 1 



of genetic engineering for new knowledge and novel applica- 
tions are wide-ranging. 

The public's anxiety over genetic engineering may have 
focused at first — in the wake of press accounts of the Asilomar 
conference — on biohazards but deeper concerns soon became 
apparent. In announcing hearings in Cambridge on Harvard's 
proposed recombinant DNA laboratory in 1976, Mayor Alfred 
E. Vellucci gave voice to the general disquiet about genetic 
engineering: "They may come up with a disease that can't be 
cured — even a monster. Is this the answer to Dr. Frankenstein's 
dream?" 16 

This "Frankenstein factor" 17 conveys the public uneas- 
iness about the notion that gene splicing might change the 
nature of human beings, compounded by the heightened 
anxiety people often feel about interventions involving high 
technology that rests in the hands of only a few. Indeed, the 
frequent repetition of the Frankenstein theme by scientists as 
well as members of the public is quite apt. 

Dr. Frankenstein was a creator of new life; gene splicing 
has raised questions about humanity assuming a role as 
creator. As a biologist and an eloquent observer of science 
notes: 

The recombinant DNA line of research is already 
upsetting, not because of the dangers now being argued 
about but because it is disturbing in a fundamental way, 
to face the fact that the genetic machinery in control of 
the planet's life can be fooled around with so easily. We 
do not like the idea that anything so fixed and stable as 
a species line can be changed. The notion that genes can 
be taken out of one genome and inserted in another is 
unnerving. 18 

Some scientists were quite unsettled by the prospect. One 
leading scientist — who had been an articulate proponent in the 
1960s of the hope for improvement that science offered to the 
"losers" in nature's "genetic lottery" — came to have grave 
reservations: 

Do we want to assume the basic responsibility for life on 
this planet — to develop new living forms for our own 
purposes? Shall we take into our hands our own future 

off by anything short of a judgment on the merits? 
Capron, supra note 13. 

16 John Kifner, "Creation of Life" Experiment at Harvard Stirs Heated 
Dispute, N.Y. Times, June 17, 1976, at A-22. 

17 Willard Gaylin, The Frankenstein Factor, 297 New Eng. J. Med. 665 
(1977). 

18 Lewis Thomas, The Hazards of Science, 296 New Eng. J. Med. 324, 
326 (1977). 



Clarifying the Issues 



15 



evolution?... Perverse as it may, initially, seem to the 
scientist, we must face the fact that there can be 
unwanted knowledge. 19 

Dr. Frankenstein's creation was a frightening monster; 
gene splicing has raised fears about strange new life forms. 
Some of these — particularly in the popular press — were far- 
fetched: 

Simply put, you take a cell from some plant or animal 
and extract the chemical (DNA) that governs all the 
physical and mental characteristics of the whole being. 
Do the same with another, totally different, plant or 
animal. Graft the two together, Presto! Shake hands with 
an orange that quacks, with a flower that can eat you for 
breakfast — or even with the Flying Nun. 20 

Other concerns with new genetic combinations were more 
immediate. Some biologists pointed to what they believed are 
the rigid natural barriers against transfer of genetic material 
between lower life forms that lack a defined nucleus (such as 
bacteria) and higher forms (such as plants and animals). 
Particularly in so-called shotgun experiments, in which the 
genetic information in an animal cell is broken into many 
pieces and each is inserted into bacteria so that it will multiply 
and can be studied, these scientists voiced concern that some 
of the genetic material might prove very harmful in its new 
setting even though a risk is not shown, or perhaps does not 
even exist, when it is part of the total package of genetic 
material in the original cell. 21 

The Frankenstein story also seems appropriate because 
the scientist there sought to control his monster, calling to mind 
the concerns raised about the distribution of power and control 
associated with gene splicing: "Each new power won by man is 
a power over man as well." 22 Of equal or greater concern was 
the view, expressed by some scientists, that even the scientists 
could not control the "monster." The basic concern about 
laboratory-generated biohazards lay with a global epidemic 
from a new pathogen that is resistant to conventional antibiot- 
ics or other therapies. As one leading scientist remarked, "You 

19 Bernard Dixon, Tinkering with genes, 235 Spectator 289 (1975) 
(quoting Robert L. Sinsheimer, Chairman, Department of Biology, 
Caltech). 

20 Susan Carson, New Origin of Species, Winnipeg Tribune, July 2, 
1979 ( Canadian Magazine), at 2. 

21 Erwin Chargaff, On the Dangers of Genetic Meddling (Letter), 192 
Science 938 (1976). 

22 C. S. Lewis, The Abolition of Man, Collier-Macmillan, New York 
(1965) at 71. 



16 



Splicing Life: Chapter 1 




4** 



can stop splitting the atom; you 
can stop visiting the moon; you 
can stop using aerosols.... But 
you cannot recall a new form of 
life." 23 If an organism can find a 
suitable niche it may survive — 
and even evolve. 

Finally, the Frankenstein 
analogy comes to mind be- 
cause of people's concern that 
something was being done to 
them and their world by indi- 
viduals pursuing their own 
goals but not necessarily the 
goal of human betterment. 

Working in his dungeon laboratory, Dr. Frankenstein 
can't be bothered by intruders. He is a genius, he has 
uncovered the secret of life, and no one can stop his 
research. Only when his monster begins to destroy does 
he realize what he has done; and by then it is too late. 24 

Mayor Vellucci of Cambridge voiced what may be a widely 
held skepticism about researchers when he declared: "I don't 
think these scientists are thinking about mankind at all. I think 
that they're getting the thrills and the excitement and the 
passion to dig in and keep digging to see what the hell they can 
do." 25 The fear was that for researchers, creating a new life 




23 Charles A. White, It's not nice to fool with mother nature, 43 
Canada & the World 10, 11 (1977) (quoting Erwin Chargaff, a 
biochemist at Columbia University). Professor Chargaff also asked 
"[H]ow about the exchange of genetic material [among microorgari- 
isms] in the human gut? How can we be sure what would happen once 
the little beasts escaped from the laboratory?" Chargaff, supra note 21, 
at 939. 

24 Arthur Lubow, Playing God with DNA, 8 New Times 48, 61 (Jan. 7, 
1977). 

25 Id. 



Clarifying the Issues 



17 



form — even a monster — would be a matter of curiosity; for the 
public, it would be an assault on traditional values. 

Thus, as the laboratory hazards of gene splicing were 
being contained, concerns about the hazards this technology 
could pose to human and social values began to bubble to the 
surface of public awareness. Some scenarios were far-fetched 
and some fears exaggerated, but in general the concerns did 
reflect an awareness that a biological revolution with far- 
reaching implications was taking place. In the Commission's 
view, there is good reason to attend to these worries, including 
those that do not involve the sorts of physical hazards that 
have received most attention thus far. New ideas can change 
the world in psychological and philosophical terms just as 
radically as new techniques can change it materially. Many 
examples exist of such changes being wrought by the discov- 
eries of science. In the sixteenth century Copernicus showed 
that the earth revolved around the sun, not the sun around the 
earth, and thus upset the notion that humanity was at the 
center of the universe. Similarly, in the last century, the theory 
of evolution propounded by Charles Darwin challenged the 
belief that human beings were uniquely created by claiming 
that they are the biological kin to other living things and that 
species have slowly differentiated through the undirected 
agency of natural selection among randomly occurring 
changes. 

The recent work in molecular genetics may again unseat 
some widely held — if only dimly perceived — views about 
humanity's place in nature and even about the meaning of 
being human. Old concepts are already being revised by some 
scientists, and it cannot be long before the new knowledge and 
new scientific powers begin to have an impact on general 
thinking. As a biochemical researcher observed: 

Once we thought the DNA of complex organisms was 
inscrutable. Now we cope with it readily. We thought of 
DNA as immovable, a fixed component of cells. Now we 
know that some modules of DNA are peripatetic; their 
function depends on their ability to move about.... We 
thought genes were continuous stretches of DNA. Now 
we know... (they)... may be interrupted dozens of times, 
and spliced together. . .when needed. We have learned 
that genes are fungible; animal genes function perfectly 
well within bacteria and bacterial genes within animal 
cells, confirming the unity of nature. We need no longer 
depend on chance events to generate the mutations 
essential for unraveling intricate genetic phenomena. 26 



26 Maxine Singer, Recombinant DNA Revisited (Editorial), 209 Science 
1317 (1980). 



18 



Splicing Life: Chapter 1 



The Commission's Study 

Some of the less tangible issues in gene splicing were 
reflected in the religious organizations' June 1980 letter to the 
President, which expressed concern that "no government 
agency or committee is currently exercising adequate oversight 
or control, nor addressing the fundamental ethical questions 
(of genetic engineering) in a major way." At its regular meeting 
in July 1980, the President's Commission took note of this 
expression of concern and decided to explore the issues 
through a hearing in September. 

At the September 1980 meeting, the Commission heard 
testimony from scientists, philosophers, and public administra- 
tors about ethical, social, and scientific aspects of the subject. 
The Commission learned that the government's jurisdiction 
over aspects of genetic engineering is both extensive and 
diverse. A Commission survey revealed no fewer than 15 
government agencies with some involvement or potential 
involvement in genetic engineering. This includes the conduct 
and funding of research related to plants, animals, and human 
beings; authority to regulate the products of gene splicing (for 
example, drugs) and its by-products (such as occupational and 
environmental risks); and a range of other activities, including 
studies of nonhuman implications of genetic technology and an 
assessment of the role of the United States in the development 
of the technology worldwide. 27 

Amidst this diversity, however, the common focus of 
government agencies has been on concrete or practical con- 
cerns involving health, environmental, and commercial conse- 
quences of the new technology. In deciding to undertake a 
study of this subject, the Commission specifically excluded the 
issue of laboratory "biohazards." This reflected the Commis- 
sion's conclusion that the latter subject was receiving consider- 
able attention and being addressed in both the public and 
private sector. Morever, it seemed more appropriate for this 
Commission to examine the broader social and ethical issues 
in genetic engineering and their significance for public policy. 

Objectives. In exploring those issues, the Commission 
found that the concerns are heterogeneous to a remarkable 
degree. Many of them are concrete and practical; others are 
vague and imprecise. Some are concerns about avoiding 
undesirable consequences of the technology or achieving its 
potential benefits, while others reflect uncertainty about 
whether a particular application of gene splicing is in fact 
beneficial or undesirable. 



27 For the results of the survey, see Appendix C, pp. 97-106 infra. 



Clarifying the Issues 



19 



The Commission also recognizes that some of the concerns 
are about future issues that might or might not occur. As 
discussed in Chapter Two, developments in this field have 
been swift. Nevertheless, predicting precisely how this technol- 
ogy will develop and how many of its potential applications 
will be realized is impossible. Direct human applications of 
gene splicing have only recently begun. Significant technical 
barriers still impede many potential applications of the tech- 
nology; sometimes even making progress reveals new hurdles. 

Although much remains to be learned in this field, 
knowledge is being acquired rapidly: in most areas of research, 
"new" means something that has been found within the past 
five years; in molecular biology, it often means something 
found within the past few months. Time and time again in the 
past ten years, the speed with which events have unfolded has 
taken well-informed observers by surprise, as noted in a major 
medical journal: 

While physicians won't be performing gene therapy on 
humans for some time, that time appears to be ap- 
proaching more rapidly every day. The tempo of applica- 
tions of new, basic technologies to clinical medicine 
continues to be astonishing. 28 
Indeed, prognostications thus far have frequently underesti- 
mated the pace of new knowledge. 

The most predictable aspect of this technology may be its 
very unpredictability. The Commission shares the view of the 
religious leaders, scientists, and others in the media, govern- 
ment, and elsewhere: a continuing exploration is needed of the 
implications of this technology that has already reshaped the 
direction of scientific research and that could revolutionize 
many aspects of life in the modern world. 

No attempt is made in this Report to resolve the myriad 
social and ethical issues generated by the ability to manipulate 
the basic material of living things. The Commission found that 
in many instances the issues had not been clearly and usefully 
articulated yet. A goal of this Report, therefore, is to stimulate 
thoughtful, long-term discussion — not preempt it with conclu- 
sions that would, of necessity, be premature. At this stage in 
the public discussion, the Commission believes there are at 
least four broad prerequisites to the development of effective 
public policy 29 : (1) educating the public about genetics and 
about the historical context of genetic manipulations; (2) 



28 Lawrence D. Grouse, Restriction Enzymes, Interferon, and the 
Therapy for Advanced Cancer, 247 J. A.M. A. 1742 (1982). 

29 The Commission uses the term "public policy" broadly to include 
not only formal laws and regulations but the many programs and 
policies of individuals and institutions that society decides are 
acceptable and not in need of direct collective intervention. Public 
policy is not limited to situations where the government has taken 



20 



Splicing Life: Chapter 1 



clarifying the concerns underlying the simplistic slogans that 
are frequently used; (3) identifying the issues of concern in 
ways meaningful to public policy consideration; and (4) 
evaluating the need for oversight and analyzing the responsi- 
bilities and capabilities for it both within and outside govern- 
ment. 

Educating the public. The United States is a country with 
ever-increasing dependence on technological and scientific 
expertise. Public participation in matters that may have 
substantial personal import often require a fundamental 
knowledge of highly specialized fields. Individuals who do not 
acquire such knowledge may hesitate to participate in the 
public debate, thinking the subject is too complicated for them 
and best left to the experts. Alternatively, public discussion 
can be misguided because people lack understanding of 
scientific facts and appreciation of the known limits and 
potentials of a new technology. The issues surrounding genetic 
engineering face both these problems. 

Public policy on genetic engineering will need to draw 
heavily on the wisdom of "experts" who have earned the 
public's trust and respect. But an informed public is also an 
essential element of a democratic decisionmaking process. As 
emphasized in the Commission's report on screening and 
counseling for genetic conditions, it is important to include 
genetics in academic curricula — beginning in early grades. 30 
Even with effective formal education on genetics, however, the 
rapid changes taking place in this field make continuing 
education essential. This Report seeks to contribute to that 
process not only by demonstrating the need for enlightened 
public discussion, but also by providing the reader with some 
basic background about this new technology. 31 Such a back- 
ground is important not only for examining significant implica- 
tions of this technology, but also for distinguishing the issues 
that merit serious attention from fantastic scenarios that have 
no scientific basis. 

The Commission also finds a second type of information 
related to gene splicing important for public discussions — an 
understanding of the context in which this new technology 



action; indeed, as the Report notes, the Commission concludes that 
many issues raised by genetic engineering are not proper subjects of 
government regulation, which is itself a public policy judgment. 

30 Screening and Counseling for Genetic Conditions, supra note 3, 
at third section of Chapter Two. 

31 Chapter Two provides technical descriptions of the recombinant 
DNA process, describes the "state of the art," and offers some 
perspective on gene splicing's potential and limitations. This informa- 
tion is intended to provide the necessary scientific groundwork for an 
understanding of the social and ethical concerns and the public policy 
considerations. 



Clarifying the Issues 



21 



arises. Gene splicing is a revolutionary scientific technique 
that recasts past ideas and reshapes future directions. Even so, 
it does not necessarily follow that all its applications or 
objectives represent a radical departure from the past. Indeed, 
the question of whether this application differs in significant 
ways from previous interventions or capacities served as an 
important guidepost for much of the Commission's discussion 
of social and ethical concerns about genetic engineering. For 
example, do the partnerships emerging between industry and 
academia in regard to gene splicing differ from past interac- 
tions in ways that give rise to new concerns or require unique 
responses? Would replacing a defective gene with a normal 
one from another person to correct a blood disorder differ 
socially and ethically from current investigations in which 
bone marrow is transplanted from one person to another for 
the same purpose? The Commission attempts to bring this 
perspective to its discussion of the issues. 

Clarifying concerns expressed in slogans, A complex and 
seemingly mysterious new technology with untapped potential 
is a ready target for simplistic slogans that try to capture vague 
fears. This is very much the case with genetic engineering. In 
Chapter Three, the Commission examines some of the slogans 
that have been invoked on both sides of the genetic engineer- 
ing controversy, and attempts to clarify and analyze the 
concerns they seem to reflect. 

A recent public opinion poll, for example, found that the 
single area of research in which restraint on scientific inquiry 
was favored is "creation of 
new life forms." 32 But what is 
meant by this term? Is bacteria 
into which a human insulin 
gene has been inserted a "new 
life form" that ought not to be 
created? Is a new hybrid corn 
offensive? Or is the fear of a 
new life form really about par- 
tially human hybrids? 

Concern is also expressed 
about gene splicing because it 
will cause human beings to 
"control evolution" or lead to 
"an alteration of the gene 
pool." But humanity's activities 
have always affected the gene 
pool. And why would tinkering 
with genes mean that evolution 
has been "controlled"? 

32 John Walsh, Public Attitude Toward Science Is Yes, but-, 215 
Science 270 (1982). 




22 



Splicing Life: Chapter 1 



On the other hand, arguments in favor of caution and 
control are sometimes met with claims of "academic freedom." 
What application does this principle have in discussing 
physical risk to other people? And how ought the value of the 
pursuit of knowledge be weighed against other values? 

Identifying the public policy issues. The diversity of 
social and ethical issues implies the need for similarly varied 
responses. A third objective of this Report, therefore, is to 
organize these issues in a way that is useful both for general 
understanding and for the formulation of sound public policy. 
The Commission has focused on the various types of uncertain- 
ties associated with the uses of gene splicing techniques: 
evaluative or ethical uncertainty; conceptual uncertainty; and 
occurrence uncertainty. 

The first type of uncertainty occurs when no societal 
consensus exists as to whether certain applications of gene 
splicing are beneficial or undesirable. Should research be 
conducted to generate means by which "positive" traits could 
be introduced into a person genetically — for example, by 
improving memory? Would this be regarded as a socially and 
ethically desirable application of the technology? Further 
uncertainty occurs because the determination of what consti- 
tutes a "defect" or "disease" varies over time and between 
cultures. 

Conceptual uncertainty refers to the fundamental change 
in concepts that this new technology can engender. As noted 
earlier, the notion that genes, once conceived of as fixed, can 
now be manipulated and exchanged has been described as 
"unnerving." The significance of this for people's conception of 
their role in the universe and even for the meaning of being 
human underlie an important set of concerns. 

Concerns like these have not typically arisen in public 
policy discussions. A limited number of implications of gene 
splicing, however, do echo issues raised by other technologies 
that have prompted generally uncontroversial public policy 
responses. The premarket testing of new drugs is one example. 
A consensus exists that certain outcomes would be beneficial, 
such as the development of safe, effective drugs, and others 
harmful, such as unsafe, ineffective drugs. The uncertainty 
involved is whether a particular outcome will occur. Policy can 
be directed specifically at promoting the desirable outcomes 
and minimizing the likelihood of harmful effects. 

Occurrence uncertainty also applies to some issues that 
cannot be so readily addressed. As with many new technolo- 
gies, the full range of scientific effects of gene splicing cannot 
now be predicted with complete certainty. And those effects 
will be expressed in a future that cannot be known in advance. 

Decisions made about the future of this technology and its 
applications will need to be made with reference to the varied 



Clarifying the Issues 



23 



types of risks and uncertainties at stake in gene splicing. 
Chapter Three attempts to organize the issues in ways that will 
foster the development of effective public policy. 

Evaluating the need for oversight. Having set out the 
types of risks posed by gene splicing, the Commission then 
considers the need for oversight of these issues. A variety of 
mechanisms, involving both the government and the private 
sector, are possible. One common feature unites all those that 
seem appropriate to the Commisson: they draw on, but are not 
controlled by, gene splicing experts. 

The Process of Study. At its July 1980 meeting, the 
Commission decided that its initial response to the religious 
leaders' concerns about government oversight would be to 
survey governmental agencies about their activities in this 
field. With the aid of a special consultant, a review of the field 
was also prepared for the Commissioners. 

A portion of the September 1980 meeting was devoted to 
reports by representatives of the most actively involved 
Federal agencies. In addition, the scientific prospects for, and 
ethical implications of, the use of genetic engineering in human 
beings were discussed by several invited witnesses. The 
Commission decided at that time to add this study to those 
mandated, according to its statutory authority to do so. 33 
During the following two years, the issue was discussed by the 
Commission at a number of its meetings. 

To assist in preparing this Report, the Commission assem- 
bled a diverse panel that included representatives from 
medicine and biology, philosophy and ethics, law, social 
policy, and the private industrial sector. 34 These consultants 
held a series of meetings with Commissioners and staff on the 
direction of the Commission's work in this area and the issues 
to be addressed. A preliminary analysis of the issues was 
prepared for discussion by the Commission in July 1981. This 
and subsequent drafts were submitted to some members of the 
panel, and comments were also received from other scientists 
and expert observers of the developments of genetic engineer- 
ing. 

Several knowledgeable people were invited to discuss the 
draft Report with the Commissioners at a hearing on July 10, 
1982, at which time preliminary approval was given to a 
portion of the Report, subject to a number of suggested changes 
and additions. A revised draft was reviewed by the Commis- 
sion at its November 12, 1982, meeting and approved, subject to 
several editorial changes. 



33 42 U.S.C. § 300v-l(a)(2). 

34 For a list of the panel members, see Appendix D, pp. 107-10 infra. 



The Dawn of a 
New Scientific Era 



Many of the questions raised about genetic engineering 
cannot be explored without some understanding of the techni- 
cal aspects of contemporary genetics and cell biology. Lack of 
information — or misinformation — not only provokes unwar- 
ranted fears but may even mean that legitimate and important 
questions remain unasked. Yet most Americans have had little 
formal training in biology, let alone in the specialized fields, 
such as micro- and molecular biology, that are involved in 
genetic engineering. Although a brief synopsis is plainly no 
substitute for a detailed education, some background may be 
helpful for nonspecialist readers. This chapter of the Report is 
intended, then, to explain a few essential concepts, to describe 
several of the most important techniques of genetic engineer- 
ing, and to show how rapidly this field is moving toward direct 
human applications. 

Discovering Life's Mysteries 

What is remarkable about the science of gene splicing is 
not that it seems strange to laypeople — for all science is arcane 
to those who do not specialize in its study — but rather how 
unfamiliar it would be for the geneticists of even one genera- 
tion ago. The existence of discrete inherited factors (later 
called genes) was postulated in 1865 by Gregor Mendel, a 
Moravian abbot who studied the patterns of inheritance in pea 
plants; his important work relied, however, on inferences about 
genes, not knowledge about their structure or functioning. 
Mendel's work lay forgotten until the beginning of this century, 
when the techniques of classical genetics were developed and 
physicians began to apply genetic knowledge in diagnosing 
conditions and in advising people about the conditions known 
to follow Mendelian patterns. Fifty years passed before Francis 



26 



Splicing Life: Chapter 2 



Crick and James Watson proposed the double helix as the 
structure for deoxyribonucleic acid (DNA), which is sometimes 
called the "master molecule of life" since almost all living 
things — including plants, animals, and bacteria — possess it. 
And the basic technique of gene splicing — a method for cutting 
and reuniting DNA — is itself only a decade old. 1 

Equally remarkable is that many new discoveries point to 
further unanswered — and perhaps even unanticipated — ques- 
tions. The humbling reality of human ignorance is as relevant 
for those in industry and government who sponsor and regulate 
scientific research as it is for those who engage in that 
research. Any attempt to unravel more of life's mysteries can 
lead in unexpected directions, with unknown risks and bene- 
fits. The choices made about proceeding in one direction rather 
than another — or whether to proceed at all — are not simply 
matters of original scientific insight or intuition nor even of 
taking the "next logical scientific step." They also depend upon 
the judgment of individual scientists, laboratory directors, and 
public and private sector sponsors, drawing on analogy and 
conjecture, educated by experience, and reflecting personal 
and institutional values. 2 

Cells and Genes. The human body is made up of billions of 
cells. Each cell has a particular function — cells in the gastroin- 
testinal tract produce enzymes that digest food, bone cells 
provide structural support, and so forth. In spite of their 
markedly varied functions, most cells share the same structural 
organization — they have a nucleus, where the genetic informa- 
tion is stored, and cytoplasm, where the specialized products 
of the cell are made (see Figure 1). 

It has been thought that all cells in an organism normally 
contain exactly the same genetic information, with the excep- 
tion of the germ cells (sperm and eggs), which carry only half. 
This information is located on individual packets called 
chromosomes, which come in pairs, half derived from each 
parent. Every species of plant or animal has a characteristic 
number of chromosomes. Humans usually have 23 pairs, or a 
total of 46; the germ cells have 23 chromosomes, one from each 
pair, while the somatic cells (the rest of the cells in the body) 



1 For a history of developments in biochemical and molecular genet- 
ics, see Horace Freeland Judson, The Eighth Day of Creation, Simon 
and Schuster, New York (1979). 

2 Thus, the underlying issue in the recombinant DNA research 
debate is the accommodation of knowledge-thrust and the 
public interest. Shall unfolding knowledge determine our de- 
sired future or shall our hoped-for future contribute to choices 
regarding the direction of knowledge-thrust? 
Clifford Grobstein, Regulation and Basic Research: Implications of 
Recombinant DNA, 51 S. Cal. L. Rev. 1181, 1199 (1978). 



A New Scientific Era 



27 



Figure 1: Cell Structure 




helix) 

contain a full set of chromosomes. Recent studies have shown 
that the genetic information is rearranged in some cells; thus 
far, these findings are limited to the antibody-producing cells. 3 

Each chromosome includes a long thread of DNA, 
wrapped up in proteins. DNA is made up of chemicals called 
nucleotides, consisting of one small sugar molecule, one 
phosphate group, and one of four nitrogenous bases, which can 
be thought of as the four letters in the genetic alphabet [A, G, T, 
and C]. 4 DNA consists of two strings of nucleotides lined up 

3 Lymphocytes, the cells that produce antibodies (proteins that protect 
vertebrates from harm by foreign invaders such as viruses and 
bacteria), engage in a form of natural recombination whereby the 
DNA segments needed to construct antibody genes combine in many 
different ways. Therefore, each clone of lymphocyte cells, which 
protects against a different invader, has a somewhat different 
configuration of genes than the other cells in the organism. See 
Maxine Singer, The Genetic Program of Complex Organisms, in 3 The 
Outlook for Science and Technology: The Next Five Years, Nation- 
al Academy Press, Washington (1982) at 1, 24-25. 

4 The four letters are from the name of the base in the nucleotide: A for 
adenine, G for guanine, T for thymine, and C for cytosine. 



28 



A New Scientific Era 



Figure 2: Replication of DNA 



Old Old 




When DNA replicates, the original strands unwind and serve as 
templates for the building of new complementary strands. The daughter 
molecules are exact copies of the parent, with each having one of the 
parent strands. 

Source: Office of Technology Assessment. 

next to each other like two sides of a zipper — the phosphates 
and sugars forming the ribbons and the nitrogenous bases 
acting like the interlocking teeth. The two strands are twisted 
around each other in a spiral fashion, forming what Crick and 
Watson in 1953 labeled a double helix. Each nucleotide is 
matched with another, to form a pair. That is, the two sides of 
the zipper can fit together in only one way: A paired with T, 
and G with C. 



Clarifying the Issues 



29 



When a cell divides into two daughter (or progeny) cells — 
a process called replication — a complete and faithful copy of 
the genetic code stored on each chromosome is usually 
transmitted to each daughter cell. Each half of the zipper acts 
like a template for the creation of its zipper-mate by drawing to 
itself free nucleotides, which then line up according to the A-T 
and G-C pattern (see Figure 2). 

Not all the DNA in chromosomes seems to have a function. 
The portions with the coded instructions to the cell to perform 
a particular function (usually to manufacture one particular 
protein) are called genes. Within the gene are the actual coding 
regions (called exons), between which are DNA sequences 
called introns. Genetic information is transferred from the 
DNA in the nucleus to the cytoplasm by RNA (ribonucleic 
acid), which is a copy of one strand of the DNA. During this 
transfer, the introns are spliced out of the RNA. The resulting 
RNA messengers pass through the cell's protein-synthesizing 
machinery (called ribosomes), like a punched tape running 
through a computer to direct a machine's operation. 

Proteins — the hormones, enzymes, connecting material, 
and so forth that give cells and organisms their characteris- 
tics — are made up of amino acids. The information carried by 
the RNA determines how the amino acids combine to make 
specific proteins. There are 20 amino acids, each one deter- 
mined by a specific combination of three of the nucleotide 
"letters" into a "codon." On average, each gene contains 
slighty more than 300 codons. 

Although all cells in an organism carry basically the same 
genetic material in their nuclei, the specialized nature of each 
cell derives from the fact that only a small portion of this 
genetic material (about 5-10%) is active in any cell. In the 
process of developing from a fertilized egg, each type of cell 
switches on certain genes and switches off all the others. 
When "liver genes" are active, for example, a cell behaves as a 
liver cell because the genes are directing the cytoplasm to 
make the products that allow the cell to perform a liver's 
functions, which would not be possible unless all the genes 
irrelevant to a liver cell, such as "muscle genes," were turned 
off. 

Accidents and Diseases. Occasionally — perhaps because 
of an error that occurs for some unexplained reason when the 
cell replicates or because of an outside influence such as a 
virus or radiation — the specific sequence in a DNA molecule is 
altered by a change of one or more nucleotides. Such a change 
is called a mutation. If a mutation occurs in a gene that is 
active in that cell, the cell will produce a variant protein, as 
will its daughter cells since they will inherit the same mutation. 
If other cells of the same type continue to perform their 
functions properly, the existence of a small amount of variant 
protein will usually have no adverse effects on the individual. 



30 



Splicing Life: Chapter 2 



Some mutations, however, are very harmful; for example, a 
defective protein can be lethal, or a malignant tumor can result 
from a mutation that alters a gene in a single somatic cell. 

Mutations that occur in somatic cells only affect the 
progeny of that mutant cell, so that the effects of such 
mutations are restricted to the individual in whom they occur. 
In the germ cells, however, mutations result in the altered DNA 
being transmitted to all cells — somatic and germinal — of an 
offspring. Inherited mutations that result in deleterious effects 
are termed genetic diseases. Even though an inherited mutation 
is present in the DNA sequence of all the body cells, it only 
affects the function of those specialized cells that manufacture 
the defective product. For example, a mutation in the gene for 
rhodopsin (a protein necessary for vision) may result in color 
blindness, but since the gene is only active in cells in the eye it 
has no other known effects on a color-blind individual. 

The Technology of Gene Splicing 

Gene splicing techniques have been understood by scien- 
tists for only a decade. During that time, they have been used 
primarily in microorganisms. Though experiments with higher 
animals indicated the possibility of using gene splicing for 
human therapy and diagnosis, numerous hurdles had to be 
crossed before such steps could be taken. Recent research has 
cleared some of those hurdles, and work is under way that may 
conquer the rest much sooner than was thought possible even 
two years ago, when the Commission began this study. 

Recombinant DNA Techniques. It was once thought that 
genetic material was very fixed in its location. Recent findings 
demonstrate that genetic recombination (the breaking and 
relinking of different pieces of DNA) is more common between 
and within organisms — from viruses and bacteria to human 
beings — than scientists realized. In fact, genetic exchange is a 
mechanism that may, in evolutionary terms, account for the 
appearance of marked variations among individuals in a given 
species. 5 

If DNA replication were the only mechanism for the 
transfer of genetic information, except for rare instances of 
mutation each bacterium would always produce an exact copy. 
In fact, three general mechanisms of genetic exchange occur 
commonly in bacteria. 6 The first, termed transduction, occurs 
when the genetic material of a bacteriophage (a virus that 



5 Raoul E. Benveniste and George J. Todaro, Gene Transfer Between 
Eukaryotes, 217 Science 1202 (1982). 

6 In higher organisms that reproduce sexually, a high degree of genetic 
variation is produced by the normal process of crossing-over of genes 
in the germ cells. Crossing-over, like the other processes, involves the 
formation of new combinations of genes. 



A New Scientific Era 



31 



Figure 3: Transduction: The Transfer of Genetic Material in 
Bacteria by Means of Viruses 



Bacterial 

Empty chromosome New virus 
Bacterium vira i coat fragments particles 

VirusV^/ ViralX^y Cell V^^Infection^^ 

DNA breakdown \ 

New 
bacterium 

In step 1 of viral transduction, the infecting virus injects its DNA into the 
cell. In step 2 when the new viral particles are formed, some of the 
bacterial chromosomal fragments, such as gene A, may be accidently 
incorporated into these progeny viruses instead of the viral DNA. In step 
3 when these particles infect a new cell, the genetic elements 
incorporated from the first bacterium can recombine with homologous 
segments in the second, thus exchanging gene A for gene a. 

Source: Office of Technology Assessment. 



infects bacteria) enters a bacterium and replicates; during this 
process some of the host cell's DNA may be incorporated into 
the virus, which carries this DNA along when it infects the next 
bacterium, into whose DNA the new material is sometimes 
then incorporated (see Figure 3). 

In a second process, called conjugation, bacterial DNA is 
transferred directly from one microorganism to another. Some 
bacteria possess plasmids, small loops of DNA separate from 
their own chromosome, that give the bacteria the ability to 
inject some of their DNA directly into another bacterium (see 
Figure 4). And third, bacterial cells can also pick up bits of 
DNA from the surrounding environment; this is called transfor- 
mation. 

These mechanisms — naturally occurring forms of gene 
splicing — permit the exchange of genetic material among 
bacteria, which can have marked effects on the bacteria's 
survival. The rapid spreading of resistance to antibiotics, such 
as the penicillin-resistance in gonorrhea bacteria and in 
Hemophilus influenzae (the most frequent cause of children's 
bacterial meningitis), documents the occurrence of genetic 
transfers as well as their benefit, from a bacterial standpoint. 

The basic processes underlying genetic engineering are 
thus "natural" and not revolutionary. Indeed, it was the 
discovery that these processes were occurring that suggested 
to scientists the great possibilities and basic methods of gene 



32 



Splicing Life: Chapter 2 



Figure 4: Conjugation: The Transfer of Genetic Material 
in Bacteria by Mating 



Plasmid Plasmid 




In conjugation, a plasmid inhabiting a bacterium can transfer the 
bacterial chromosome to a second cell where homologous segments of 
DNA can recombine, thus exchanging gene B from the first bacterium 
for gene b from the second. 

Source: Office of Technology Assessment. 

splicing. What is new, however, is the ability of scientists to 
control the processes. Before the advent of this new technolo- 
gy, genetic exchanges were more or less random and occurred 
usually within the same species; now it is possible to hook 
together DNA from different species in a fashion designed by 
human beings. 

The key to human manipulation of DNA came with the 
discovery, in the early 1970s, of restriction enzymes. 7 Each 
restriction enzyme, of which about 150 have so far been 
identified, makes it is r. ossible to cut DNA at the point where a 
particular nucleotide sequence occurs. The breaks, which are 
termed "nicks," occur in a staggered fashion on the two DNA 
strands rather than directly opposite each other. Once cut in 
this fashion, a DNA strand has "sticky ends"; the exposed ends 
are ready to "stick" to another fragment that has been cut by 
the same restriction enzyme (see Figure 5). Once the pieces are 
"annealed" and any remaining gaps are ligated, the "recombi- 
nant DNA" strand will be reproduced when the DNA repli- 
cates. 

Recombinant DNA studies have been performed primarily 
in laboratory strains of the bacterium Escherichia coli, which 
is normally present in the human intestine. This bacterium 
possesses only one small chromosome, but it may also contain 
several ring-shaped plasmids. Plasmids turn out to be useful 
vehicles (or vectors) by which a foreign gene can be introduced 



7 These enzymes, which make it possible to cut DNA at predetermined 
places, exist as part of the defense system that bacteria use to respond 
to foreign DNA (from a virus, for example). Restriction enzymes cut 
the DNA of the invader into small pieces, while another substance 
protects the bacteria's own DNA from getting sliced. 



A New Scientific Era 



33 



Figure 5: Creation of "Sticky Ends" by a Restriction Enzyme 



Nick 

i 

-X-X-X-G A-A-T-T-C-X-X-X- 
• ••• •••• 

-X-X-X-C-T-T-A-A^G-X-X-X- 

Nick 

One restriction enzyme produced by E. coJi, named Eco RI, recognizes 
the DNA sequence -G-A-A-T-T-C- on one strand and -C-T-T-A-A-G- on 
the other. It does not cut clearly across the two strands, however, but 
between the G and A on both strands, leaving each with exposed bases 
that can stick to another DNA strand that has been cut in the same 
fashion and also has an exposed -A-A-T-T- sequence. 

into the bacterium. A plasmid can be broken open with 
restriction enzymes, and DNA from another organism (for 
example, the gene for human insulin) can then be spliced into 
the plasmid (see Figure 6). After being resealed into a circle, 
the hybrid plasmid can then be transferred back into the 
bacterium, which will carry out the instructions of the inserted 
DNA (in this case, to produce human insulin) as if it were the 
cell's own DNA. In addition, since plasmids contain genes for 
their own replication independent of bacterial DNA replica- 
tion, many copies of the hybrid plasmid will be present in each 
E. coli cell. The end result is a culture of E. coli containing 
many copies of the original insulin gene and capable of 
producing large amounts of insulin. 

The process of isolating or selecting for a particular gene is 
commonly called cloning a gene. A clone is a group all of 
whose members are identical. Theoretically, this technology 
allows any gene from any species to be cloned, but at least two 
major steps must be taken to make use of this technology. First, 
it is quite easy to break apart the DNA of higher organisms and 
insert fragments randomly into plasmids — a so-called shotgun 
experiment — but identifying the genes on these randomly 
cloned pieces or selecting only those recombinant molecules 
containing a specific gene is much more difficult. Because 
scientists do not yet fully understand what controls gene 
regulation, inducing expression of the inserted genes has been 
a second major hurdle. Recently, scientists have been success- 
ful in getting a recombinant gene to function in multicell 
animals and, with the discovery of what are termed transposa- 



34 



Splicing Life: Chapter 2 



Figure 6: Splicing Human Gene into Plasmid 



E. coli bacteria, taken 
from human intestine 



Pancreas 



Nucleus 



Plasmid 




E. coli 

chromosome 



/ Plasmid removed 
from E. coli 



Plasmid cut open by 
restriction enzyme 
at a specific site 




Human cell 



Strand of DNA from human cell 



Human DNA cut 
into pieces 
\f by restriction 
enzyme 




Recombinant DNA 
(hybrid plasmid) 



Human insulin gene 



■\ Hybrid plasmid 

i inserted into E. coli cell 




Source: President's Commission 



Bacteria with hybrid plasmid replicate, creating clone 
capable of producing insulin 



A New Scientific Era 



35 



ble elements, even in correcting a defect in some fruit flies' 
genes. 8 This development serves as a reminder that many 
technical barriers that loom large are rapidly overcome. Of 
course, new knowledge sometimes also reveals further, unan- 
ticipated technical difficulties to be overcome. 

Cell Fusion. Cutting apart DNA chains is not the only way 
that scientists can transfer genetic material from one cell to 
another. Cell fusion, which involves the breaking down of cell 
membranes and the merging of two different types of cells, can 
also be regarded as a form of genetic engineering although it 
does not involve direct manipulation of DNA segments. It is 
being vigorously explored by biomedical scientists who are 
attempting to map the specific location of human genes on 
chromosomes and to learn about cellular development and 
differentiation. These advances should ultimately lead to 
better understanding, diagnosis, and treatment of various 
diseases and cancers. 

For example, researchers can now produce what are 
termed monoclonal antibodies. Antibodies are substances 
produced by the body to fight foreign substances, such as 
microbial "invaders." Unlike other methods of production, cell 
fusion techniques have provided especially pure antibodies 
against a particular invader (or "antigen"). They are called 
monoclonal because they are produced by a clone of cells 
descended from a single fabricated original. First, scientists 
stimulate a mouse to produce antibodies by injecting it with a 
protein. White blood cells containing an antibody aimed at 
fighting the "disease" (which is how the mouse's immune 
system regards the injected proteins) are then fused chemically 
with malignant cells through a process that involves dissolving 
and regenerating the cells' outer membranes. This combina- 
tion — called a hybridoma — inherits the cancer cells' ability to 
proliferate rapidly and indefinitely and the blood cells' capaci- 
ty to produce the antibody. Scientists can thus generate a huge 
clone of cells, which can provide a large amount of the desired 
antibody. 

Cell fusion is not limited to the creation of hybridomas. 
The 1980 Supreme Court decision that sanctioned the patenting 
of "new life forms" did not involve recombinant DNA tech- 
niques but rather the insertion into bacteria of four naturally 
occurring plasmids capable of degrading four components of 
oil. 9 The Court held the resulting microorganism was patenta- 
ble because it was new (as bacteria in nature did not 
incorporate all four of the plasmids at once) and useful (as the 



8 Gerald M. Rubin and Allan C. Spradling, Genetic Transformation of 
Drosophilia Germ Line Chromosomes, 218 Science 348 (1982). 

9 Diamond v. Chakrabarty, 447 U.S. 303 (1980). 



36 



Splicing Life: Chapter 2 



genetically engineered bacteria could break down oil spills 
more rapidly and efficiently). 

Genetically Engineered Medical Products 

The ability to "engineer" new capabilities into microorga- 
nisms has now been used to develop therapeutic and diagnos- 
tic agents for human use. This is the first, and thus far the 
major, use of gene splicing in the medical sphere. 

Production of Drugs and Biologies. Most living cells are 
protein factories, "manufacturing" products according to the 
"code" of those genes in the cells that are active. Through the 
use of gene splicing techniques, bacterial cells can be altered 
so that they will turn out the product encoded by a foreign gene 
that has been spliced into a plasmid in the bacteria. When such 
bacteria are then grown in large-scale fermentation broths, 
huge quantities of valuable medical products are expected to 
be harvested because bacteria multiply very rapidly — a single 
bacterium can produce more than a billion copies of itself in 15 
hours. 

The list of medically useful products that may be obtained 
through gene splicing techniques is long; a few applications 
will serve to illustrate. The new technology has already led to 
the production of several useful human hormones, including 
human growth hormone to treat dwarfism. To date, many 
desirable medical products had to be isolated and purified 
biochemically from natural sources. For example, the insulin 
consumed by diabetics in this country is isolated from the 
pancreata of over 80 million cows and pigs each year. Since the 
supply of pancreas glands is dependent on the demand for beef 
and pork, gene splicing offers a more stable supply of this 
essential hormone. Insulin produced with recombinant DNA 
methods has recently been approved for sale in Great Britain 
and the United States. 10 

It is predicted that gene cloning of many human hormones 
will soon be accomplished. Other useful products made by the 
human body in small quantities are being worked on. For 
example, there is interest in producing urokinase, which 
dissolves blood clots and may be useful for treating thrombo- 
phlebitis, and anti-hemophilic factor, which is required for 
blood clotting and is needed to treat hemophilia. 

Interferon is another natural product that has attracted 
much interest for its apparent ability, discovered in 1957, to 
prevent a virus from proliferating after it invades a body. By 
the mid-1970s, laboratory evidence suggested that interferon 
might curtail the spread of certain cancers. Clinical tests and 



10 Lawrence K. Altman, U.S. Unit Backs Human Insulin for the 
Market, N. Y. Times, Oct. 30, 1982, at A-l. 



A New Scientific Era 



37 



therapeutic application proceeded slowly, however, because 
supplies of interferon were very limited and extremely costly. 
Most interferon was extracted from cells of donor blood 
samples in minute quantities, usually laced with impurities. 
The cost of treating one cancer patient is between $20,000 and 
$30,000. Therefore, great enthusiasm greeted the prospect of 
using recombinant DNA techniques to create interferon (a 
process that also revealed that interferon is not a single 
substance but a family of related ones, each of which may be 
effective against certain problems). 11 

Interferon produced through gene splicing is now being 
tested in clinical trials. Although research to date on interferon 
obtained by the traditional methods suggests that its potential 
as the proclaimed "wonder drug" was greatly overstated, the 
use of gene splicing to produce pure samples in larger 
quantities offers an opportunity to clarify the many questions 
that have arisen in the limited existing clinical tests and to 
resolve some of the issues regarding the use of human 
interferon in cancer treatment. 

Another area of widespread applicability is in the produc- 
tion of useful vaccines. Presently, a weakened strain of a virus 
must be grown in tissue culture, a tedious chore, before people 
can be inoculated. There is always a risk that the virus used for 
inoculation may change into a more virulent strain and 
actually produce the disease it was meant to protect against. 
Genetic engineering would allow large-scale production of 
pure viral components (that is, the protein "coat" of a virus, 
which is how the body recognizes the virus as a foreign 
invader and sends out its antibodies to attack it). Such 
components, being only part of the virus, should be much safer 
while still conferring immunity. Within the past several years, 
researchers at MIT reported the cloning of the gene for the 
protein coat of polio virus and an international team an- 
nounced it had used recombinant DNA technology to produce 
the surface antigen associated with the hepatitis B virus. 12 
Researchers are also exploring the development of vaccines for 
certain cancers associated with particular viruses, such as the 
Epstein-Barr virus and hepatitis B virus, using the antigenicity 
of the outer coat of the viruses. 13 



11 Marjorie Sun, Interferon: No Magic Bullet Against Cancer, 212 
Science 141 (1981); Michael Edelhart, Putting Interferon to the Test, 
N.Y. Times, April 26, 1981 (Magazine), at 30. 

12 V. R. Racaniello and D. Baltimore, Cloned Poliovirus Complementa- 
ry DNA is Infectious in Mammalian Cells, 20 Science 916 (1981); P. 
Charnay et ah, Biosynthesis of Hepatitis B. Virus Surface Antigen in 
Escherichia ColL, 286 Nature 893 (1980). 

13 Baruch S. Blumberg et al, The Relation of Infection With the 
Hepatitis B Agent to Primary Hepatic Carcinoma, 81 Am. J. 
Pathology 669 (1975); Mark Pasek et al, Hepatitis B Virus Genes and 
Their Expression in E-Coli, 282 Nature 575 (1979). The production of 



38 



Splicing Life: Chapter 2 



Cancer Diagnosis and Therapy. A major line of research in 
oncology today employs genetic engineering technology — in 
the form of cell fusion — to harness the potential power of 
monoclonal antibodies in the fight against cancer. Because the 
human body synthesizes such a huge variety of antibodies, the 
hope is that antibodies can be produced that are highly 
targeted for particular tumors and especially for the few cells 
that remain when a tumor is surgically excised or irradiated. 
Antibodies tagged with markers (such as trace amounts of 
radioactive chemicals) can also act like probes, permitting 
better diagnosis of the location and size of cancers. 

Thus far, physicians have reported on only a few dozen 
cancer patients treated with monoclonal antibodies. The 
notable results of one of these early trials were announced in 
March 1982: a man with a rare malignancy that had defied 
previous treatment received a specially designed antibody and 
within weeks showed dramatic improvement, including the 
disappearance or diminution of the tumors that had proliferat- 
ed throughout his body. 14 Although proof of effectiveness and 
an understanding of side effects must await years of clinical 
testing, the theory behind the technique is attractive: target a 
particular cell for attack by an antibody, or by a chemical 
poison attached to the antibody, rather than rely on current 
methods that involve radiation and chemicals that can have 
devastating effects on the body's normal cells while they 
attempt to destroy all the cancer cells. 

Genetic engineering is also being used by biomedical 
scientists who are trying to understand and control the 
recently identified "oncogenes" that apparently direct the wild 
proliferation of cells that creates a tumor. Sometimes the 
genetic error involved appears to be inherited; other times it 
apparently results from damage during a person's lifetime from 
chemicals, radiation, or a virus. Gene splicing may permit the 
genetic error to be identified early and even to be treated, 
although such procedures are not imminent. 

Genetic Screening and Diagnosis 

One spin-off of recombinant DNA technology exploits the 
specificity of restriction enzymes to help diagnose the exis- 



vaccines for diseases affecting domestic animals is also being very 
actively pursued. Other agricultural uses (engineering new traits in 
plants and animals rather than breeding for these traits), as well as 
industrial and mining uses of gene splicing, are being vigorously 
explored in academic and commercial laboratories in this country and 
elsewhere. Office of Technology Assessment, U.S. Congress, Impacts 
of Applied Genetics — Micro-Organisms, Plants, and Animals, U.S. 
Government Printing Office, Washington (1981). 

14 Richard A. Miller et ah, Treatment of B-Cell Lymphoma with 
Monoclonal Anti-Idiotype Antibody, 306 New Eng. J. Med. 517 (1982). 



A New Scientific Era 



39 



tence of or the carrier status for a wide range of genetic 
disorders that until now have not been readily diagnosable. 15 
The technique holds particular promise for prenatal tests and 
for diagnosis of late-onset disorders such as Huntington's 
disease. Recombinant DNA techniques allow the DNA of a 
gene itself to be assessed, unlike previous techniques that 
necessitate waiting for the gene's product (that is, an identified 
protein) to be manufactured. 

"Restriction enzyme sites" are the specific sequences in 
the DNA at which one of the 150 known restriction enzymes 
recognizes and cuts the DNA molecule. Restriction enzymes 
can provide the basis for a useful assay for a particular gene in 
two ways: (1) if the molecular variation in the DNA of the gene 
is known and coincides with the cutting site for a particular 
restriction enzyme on the gene in question, or (2) if the 
restriction enzyme site lies on a variant DNA "marker" gene 
adjacent to the gene of interest, with which it is linked. Both 
techniques are based upon the fact that specific restriction 
enzymes cut the DNA into fragments of a characteristic length. 
If the sequence of the nucleotides is "abnormal" at a point that 
a restriction enzyme would cut, the enzyme will not cut there 
but at the next enzyme site, thereby producing a DNA fragment 
of unusual length. 16 

Mutations in the nucleotide sequence can have harmful, 
neutral, or beneficial consequences. Those that are deleterious 
put an organism at a disadvantage for survival and reproduc- 
tion; hence they usually appear at very low frequencies in a 
population. On the other hand, some mutations persist with 
some frequency in a species. Occasionally, these variant forms 
of DNA — which are called polymorphisms — occur in the por- 
tions of the genes that actually code for proteins, apparently 
because they provide the organism with some survival advan- 
tage. Polymorphisms are more frequent in the introns or in the 
"spacer DNA" (those segments of the chromosomes that lie 
between the genes) because they do not code for proteins and 
their precise DNA sequences are thus not crucial for normal 
functioning. 

Some genes that code for variant hemoglobins are relative- 
ly frequent, such as the gene that causes sickle-cell disease. It 
is an example of a mutation that, in the heterozygous form, 
provides a selective advantage. In regions where malaria was 
prevalent, people who had one gene for sickle hemoglobin (and 



15 See, e.g., Alan E. Emery, Recombinant DNA Technology, 2 Lancet 
1406 (1981). 

16 Arlene Wyman and R.L. White, Restriction Fragment Length 
Polymorphism in Human DNA, 77 Proc. Nat'l. Acad. Sci. 6754 (1980); 
D. Botstein et ah, Construction of a Genetic Linkage Map in Man 
Using Restriction Fragment Length Polymorphisms, 32 Am. J. Human 
Genetics 314 (1980). 



40 



Splicing Life: Chapter 2 



one for normal hemoglobin) were less likely to die from 
malaria. In 1978, geneticists' understanding of the mutational 
site of the sickle-cell variant led to a direct demonstration of 
the primary gene mutation responsible for sickle-cell disease 
by using a restriction enzyme that cuts DNA at that site. 17 This 
procedure allowed the detection of the sickle mutation by an 
examination of the length of the fragments produced. Thus, 
sickle-cell anemia — which previously could be diagnosed 
prenatally only by obtaining a sample of fetal blood (a process 
that is more difficult and riskier than ordinary amniocen- 
tesis) — is diagnosable in fetal cells using recombinant DNA 
technology, although the procedure is not yet in wide clinical 
use. 

At least in the foreseeable future, scientists do not believe 
that most genetic diseases will be diagnosable by finding a 
direct correspondence between a known mutation in the gene 
and a restriction site since the nature of the DNA mutation in 
most genetic diseases remains unknown. But two new alterna- 
tive diagnostic means are now being used for a growing list of 
genetic conditions. The first, which depends on restriction 
fragment length polymorphisms, can be used even when the 
genetic mutation is not known. By using restriction enzymes to 
reveal variations in spacer DNA and in introns, scientists 
within a few years will have created a map of genetic 
landmarks on all chromosomes so that studies of genetic 
diseases can be undertaken to locate the genes that cause 
these diseases. 18 Thus, one or another DNA variant will be 
linked with each genetic disease. When such a "linkage" 
between an abnormal gene and a DNA polymorphism is used, 
the closer the restriction enzyme cutting site is to the gene, the 
more likely it is that they will be inherited together. 

To apply this technique to screening, it is necessary to do 
studies of the genes in a family and develop the linkage 
patterns between the "marker" DNA and the gene of clinical 
interest. The finding of a specific DNA pattern in an offspring 
is only significant for diagnostic purposes when a parent or 
sibling who has the genetic condition in question has also been 
typed for the linked marker. Often both parents, and some- 
times other relatives, have to be studied to interpret the 
meaning of the DNA pattern in the child. 



17 Y.W. Kan and A. M. Dozy, Antenatal Diagnosis of Sickle-Cell 
Anemia by DNA Analysis of Amniotic-Fluid Cells, 2 Lancet 910 
(1978). 

18 David T. Bishop et ah, The Number of Polymorphic DNA Clones 
Required to Map the Human Genome, in Bruce Weir, ed., Statistical 
Analysis of DNA Sequence Data (in press); Mark H. Skolnick and U. 
Francke, Report of the Committee on Human Gene Mapping by 
Recombinant DNA Techniques, 32 Cytogenetics & Cell Genetics 194 
(1982). 



A New Scientific Era 



41 



A second new method, termed oligonucleotide hybridiza- 
tion, can be used when the mutation in the gene is known but 
does not coincide with a restriction enzyme site. 19 An assay 
can be performed with relatively short synthetic DNA probes 
that will show whether the gene or the mutant is present. The 
initial research has been done in a pulmonary disorder, but the 
first general applications are likely to be in the prenatal 
diagnosis of the various beta-thalassemias. 

Although the diagnostic uses of gene splicing have engen- 
dered less controversy than the therapeutic uses (and, hence, 
receive less attention in this Report), this area of health care is 
one that recombinant DNA technology is likely to affect most 
in the immediate future. In effect, these developments will 
magnify the ethical considerations addressed in the Commis- 
sion's report on genetic screening and counseling. 20 Genetic 
engineering techniques will permit the identification of a much 
wider range of genetic traits and conditions in utero; thus, they 
may greatly broaden the demand for, and even the objective of, 
prenatal diagnosis. 

Difficult social and ethical issues will also be posed by the 
greatly enhanced ability of genetic screening to identify people 
with a susceptibility to diseases, some of which are treatable 
(such as colon cancer in patients with hereditary polyposis, or 
hemochromatosis, a disease involving a buildup of iron in the 
blood) and some of which are not (such as Huntington's 
disease). Genetic screening will probably be much more widely 
used not only in personal medical care and counseling but also 
in public health programs, insurance exams, and occupational 
or pre-employment settings as more is learned about the 
association between particular genotypes and disease suscep- 
tibility. Screening may permit individuals to obtain preventive 
medical care early or to identify those environments and 
behaviors that they ought to be especially careful to avoid. 21 



19 Savio Woo et ah, Alpha-1 Antitrypsin Deficiency and Pulmonary 
Emphysema: Identification of Recessive Homozygote by Direct Anal- 
ysis of the Mutation Site in the Chromosomal Genes, Cold Spring 
Harbor Symposium on the Application of Recombinant DNA to 
Human Disease, 1982 (in press). 

20 President's Commission for the Study of Ethical Problems in 
Medicine and Biomedical and Behavioral Research, Screening and 
Counseling for Genetic Conditions, U. S. Government Printing 
Office, Washington (1983). 

21 Eventually, medical scientists may be able to identify not only 
restriction enzyme sites that are tightly linked to known gene defects 
and some that are actually located at the exact site of a mutation, but 
also the presence or absence of genes that are responsible for other 
human characteristics, even those that would not be detectable 
through looking for their biochemical "footprints," as is now done, for 
example, in measuring the level of serum phenylalanine in screening 
for phenylketonuria (PKU). Of course, most interesting human charac- 



42 



Splicing Life: Chapter 2 



Curing Genetic Disorders 

In the immediate future, the most important applications of 
gene splicing techniques for human health will probably be in 
the creation of products — hormones, enzymes, vaccines, and so 
forth — for human consumption and in the development of 
genetic screening. But in the long run, direct use of the 
technique in humans can be expected to have an impact that is 
much more significant in terms of changing people's health and 
developmental status, and more novel and far-reaching in 
conceptual and psychological terms. During 1982, the prospect 
of direct application of gene splicing to cure human genetic 
diseases moved forward by large steps, although formidable 
hurdles remain. 

The simplest form of human gene splicing would be 
directed at single gene mutations, which are now known to 
cause more than 2000 human disorders. 22 Such a defect in just 
one gene — although each human cell has as many as 100,000 
genes — can have tragic and even fatal consequences. Existing 
treatments of genetic diseases are all palliative rather than 
curative — that is, they are merely aimed at modifying the 
consequences of a defective gene. In contrast, gene splicing 
technology offers the possibility of correcting the defects 
themselves and thus curing at least some of these diseases. 
The effects of gene splicing might be limited to the somatic 
cells of the individual being treated or might, intentionally or 
otherwise, alter the germ cells, thereby creating a change in the 
genes that would be passed on to future generations. 

Somatic Cells. The basic method proposed for using gene 
splicing on human beings is termed "gene therapy." This is 
defined as the introduction of a normal functioning gene into a 
cell in which its defective counterpart is active. If the mutant 
gene is not removed but merely supplemented, the cells may 
continue to produce the defective product alongside the normal 
product generated by the newly added gene. 

Even further in the future is a theoretical possibility, 
sometimes referred to as "gene surgery," in which not only 
would the normal gene be added but the defective gene itself 
would either be excised or its function suppressed, so that it 
would no longer send out a message for a defective product in 
competition with the message from the inserted "normal" gene. 

The technology, which researchers are now attempting to 
develop, involves four steps: cloning the normal gene, introduc- 
ing the cloned genes in a stable fashion into appropriate target 



teristics are believed to result from the interaction of the environment 
with a number of genes, rather than a single gene, which would make 
"screening" an exceedingly complex task. 

22 Victor A. McKusick, Mendelian Inheritance in Man, Johns Hopkins 
Univ. Press, Baltimore (6th ed. 1982). 



A New Scientific Era 



43 



cells by means of a vector, regulating the production of the 
gene product, and ensuring that no harm occurs to the host 
cells in the patient. Only the first step — cloning a normal 
counterpart of a defective gene — is a straightforward matter 
with current knowledge and technology. 

Introducing copies of the normal gene specifically to a 
particular set of target cells can, in theory, be achieved. Gene 
therapy offers the greatest promise for those single-gene 
defects in which an identifiable product is expressed in a 
discrete subpopulation of cells. For example, sickle-cell anemia 
and beta-thalassemia (also called Cooley's anemia) both 
involve alterations in the hemoglobin gene that is expressed in 
an accessible subpopulation of cells (that is, bone marrow 
cells) that could be removed from the body for gene treatment 
and then returned to the patient. These two diseases have 
therefore been among the early objects of attention for 
researchers designing gene therapy techniques. 23 

In most other cases, it is not practical to remove the target 
cells (such as brain cells in people with Tay-Sachs disease) for 
gene repair. A far more promising approach takes advantage of 
the distinctive properties of different cells, the unique markers 
each type of cell has on its surface. Once the unique marker for 
particular cells has been identified, it may be possible to 
construct a special "package," carrying copies of the normal 
gene, that will home in on this marker and deliver the new 
genes exclusively to the cells where the defective gene is 
active. 

Once in the cell, the normal gene may persist as an 
independent unit, like a plasmid, or may integrate itself 
randomly somewhere in the DNA. The principal problem is 
inducing the host cell to produce the proper amount of the 
desired product. 24 Lack of expression of the normal gene would 
prevent the "therapy" from being effective, whereas excess 
production could be deleterious or even fatal. Although 
transposable elements of the sort that permitted new genetic 
material to be inserted in a nonrandom fashion and properly 
expressed in the experiments with fruit flies have not yet been 
identified in human beings, a comparable set of DNA appears 
to exist in human beings. 

A final worry is that introducing a new gene may disrupt 
the functioning of the existing cells. For example, were the new 
piece of DNA to be spliced in the middle of another gene, it 
could create a gene defect that is worse than the defect the 
gene therapy was intended to correct. 



23 Richard Roblin, Human Genetic Therapy: Outlook and Apprehen- 
sions, in George K. Chacko, ed., Health Handbook, Elsevier-North 
Holland Pub. Co., New York (1979) at 103, 108-12. 

24 Jean L. Marx, Still More About Gene Transfer, 218 Science 459 
(1982). 



44 



Splicing Life: Chapter 2 



Despite these technical stumbling blocks, two attempts 
have already been made at gene therapy. The first — which 
relied on viral transduction before recombinant DNA tech- 
niques were discovered — occurred more than a decade ago 
and attracted little public attention. Several German sisters 
had a rare metabolic error that caused them to develop a high 
level of a substance called arginine in their bloodstream. Left 
uncorrected, this genetic defect leads to metabolic and neuro- 
logic abnormalities, including severe mental retardation. No 
treatment for argininemia was known, so medical researchers 
in Germany decided to take advantage of a characteristic of 
the Shope virus, which, although apparently harmless to 
human beings, causes people exposed to it to have an 
unusually low level of arginine. Researchers infected the girls 
with the virus, in the hope that it would transfer to them its 
gene for the enzyme that the body needs to metabolize 
arginine. This attempt to add new genetic material failed — that 
is, the buildup of arginine continued. 25 

The second attempt at gene therapy in human beings 
involved a controversial experiment in 1980 on patients 
suffering from beta-thalassemia. A UCLA physician removed 
bone marrow cells from a patient in Israel and another in Italy, 
mixed the cells with DNA coding for hemoglobin (in the hope 
that a normal hemoglobin gene would be stably incorporated 
into the bone marrow cells), and then returned the cells to the 
patients. The attempt apparently neither benefited nor harmed 
the patients. The investigator justified the experiment on the 
ground of previous success in transferring foreign genes into 
the bone marrow of mice. The Institutional Review Board at 
UCLA — which must give prior approval for research involving 
human subjects — had refused to give permission to proceed 
with the experiment on the ground that more animal work was 
needed. 26 The experiment drew considerable criticism from 
other scientists, who challenged the adequacy of the animal 
work. 27 NIH, which had provided the principal investigator 



25 w French Anderson, Genetic Therapy, in Michael P. Hamilton, ed., 
The New Genetics and the Future of Man, William B. Eerdmans Pub. 
Co., Grand Rapids, Mich. (1972) at 109, 118. 

26 President's Commission for the Study of Ethical Problems in 
Medicine and Biomedical and Behavioral Research, Protecting 
Human Subjects, U.S. Government Printing Office, Washington (1981) 
at 177, 182. 

27 In the opinion of Dr. Bob Williamson, a molecular geneticist at the 
University of London: 

Cline's experiments were fundamentally unethical. His own 
work on mice shows that there was no basis for hope that 
globin gene insertion into marrow cells could give clinical 
benefit at that time. [The subjects') families were given hope 
that the gene therapy might help them in their fight for survival. 



A New Scientific Era 



45 



with funding, imposed sanctions, including stripping him of 
some of his grant funds. 28 The UCLA experiment generated 
considerable discussion of the ethical issues involved in gene 
therapy beyond the facts of that case and particularly about 
the appropriate time to initiate gene therapy in humans. 29 

Popular notions regarding gene therapy range from seeing 
it as a weapon for fighting any disease to hailing it as a tool for 
changing human characteristics, including removal of a hypo- 
thetical "aggression gene" from hardened criminals. These 
notions are unrealistic. Many diseases have multigenic or 
unknown etiologies; human attributes such as kindness or 
aggression are most certainly the result of a complex interac- 
tion of multigenic and environmental factors. The forms of 
genetic treatment now being discussed would be relevant to 
such conditions only if the effects of specific genes could be 
identified and particularly if some of these genes prove to be 
major determinants, since attempts to change a number of 
genes at the same time would probably be extremely difficult. 
It is therefore highly unlikely that in the foreseeable future 
predictable changes in such attributes could be achieved 
through genetic alterations. 30 

Gene therapy carried out on somatic cells, such as bone 
marrow cells, would resemble standard medical therapies in 
that they all involve changes limited to the cells of the person 
being treated. They differ, however, in that gene therapy 
involves an inherent and probably permanent change in the 
body rather than requiring repeated applications of an outside 
force or substance. An analogy is organ transplantation, which 
also involves the incorporation into an individual of cells 
containing DNA of "foreign" origin. 

Germ-Line Cells. Thus far, attempts at gene therapy have 
focused on treating a discrete population of patients' somatic 
cells. Some researchers believe that certain forms of gene 
therapy that have been considered, such as the use of a virus to 



It is unacceptable that patients should be misled in this way. 
Bob Williamson, Gene Therapy, 298 Nature 416, 418 (1982]. See also, 
Nicholas Wade, UCLA Gene Therapy Racked by Friendly Fire, 210 
Science 509 (1980). 

28 Marjorie Sun, Cline Loses Two NIH Grants, 214 Science 1220 (1981). 

29 A scientist and an ethicist at the National Institutes of Health 
suggest that three conditions should be met in animal studies before it 
is ethical to initiate trials of human gene therapy: (1) the new gene 
should be put into target cells and remain in them; (2) the new gene 
should be regulated appropriately; and (3) the presence of the new 
gene should not harm the cell. W. French Anderson and John C. 
Fletcher, Gene Therapy in Human Beings: When is it Ethical to 
Begin?, 303 New Eng. J. Med. 1293 (1980). See also, Arno G. Motulsky, 
Impact of Genetic Manipulation on Society and Medicine, Science (in 
press). 

30 Williamson, supra note 27. 



46 



Splicing Life: Chapter 2 



carry the desired gene to the patient's cells, might also affect 
germinal cells. Furthermore, gene therapy could also be applied 
to fertilized human eggs (zygotes) in conjunction with in vitro 
fertilization techniques. 31 Whereas the effects of genetic thera- 
py on somatic cells would be expected to be limited to the 
individual patient treated, DNA therapy of fertilized eggs 
would probably affect all cells — including the germ cells — of 
the developing embryo; assuming normal birth, development, 
and reproduction, the individual would then pass on the 
altered gene to his or her offspring according to Mendelian 
rules. Zygote therapy would thus involve an alteration of the 
genetic inheritance of future generations and a significant 
departure from standard medical therapy. 

To date, genetic engineering experiments using zygotes 
have been conducted for academic rather than therapeutic 
reasons. Several laboratories are currently working on ferti- 
lized mouse eggs. In one experiment, mice developed from 
zygotes injected with the rabbit hemoglobin gene were report- 
ed to contain rabbit hemoglobin in their red blood cells. 32 The 
medical significance is obvious. In a case where both parents 
are carriers of a particular recessive disorder the risk of an 
affected child is one in four. But if the relevant normal gene 
could safely be introduced in vitro to a fertilized egg of that 
couple, the individual who resulted from the egg would not 
have the disease and none of his or her descendants would be 
at risk for that disease. 

Zygote therapy differs significantly from gene therapy on 
somatic cells in several ways. First, from the standpoint of the 
individual it may be useful in the treatment of genetic diseases, 
like cystic fibrosis, that affect many tissues — lungs, pancreas, 
intestines, and sex organs — rather than a discrete, accessible 
subpopulation of cells. Successful treatment at a very early 
stage of development would confer "good" genes to all the 
organs of an afflicted individual. Second, from the societal 
standpoint, such therapy if ever practiced on a vast scale could 
potentially reduce the overall frequency in the population of 
genes that usually have deleterious consequences, such as the 
sickle-cell gene. 

Although zygote therapy may hold great promise, it is also 
fraught with technical risks and uncertainties. First of all, the 



31 The approach would involve the following: (1) isolating and 
amplifying the desired gene by standard recombinant DNA tech- 
niques, (2) removing a mature ovum from a woman and fertilizing it in 
vitro, (3) injecting copies of the cloned gene into the fertilized egg 
(zygote) using microsurgical techniques, and (4) implanting the geneti- 
cally altered zygote into the woman's uterus. 

32 Thomas E. Wagner et ah, Microinjection of a Rabbit B-globin Gene 
into Zygotes and Its Subsequent Expression in Adult Mice and Their 
Offspring, 78 Proc Nat'l. Acad. Sci. 6376 (1981). 



A New Scientific Era 



47 



technique itself is largely unproven, even with laboratory 
animals. For example, the success rate of microinjecting genes 
into mouse embryos remains low. Increasing the amount of 
DNA injected into a zygote makes it more likely that a gene 
will be incorporated, but it also increases the mortality rate of 
embryos. Microinjection of DNA into zygotes is obviously not a 
benign procedure. 

The second major technical drawback at present is that 
transferred genes integrate randomly in the genome. Depend- 
ing on the site of integration and perhaps the physiological 
state of the embryo, some of the foreign genes may be 
expressed and others not. Thus far, in experiments with mice, 
genes are rarely expressed in a tissue-specific way. 33 Even 
then, expression of the microinjected foreign gene in somatic 
tissue has not resulted in stable inheritance of that expres- 
sion, 34 which is essential if the purpose is to introduce a new 
trait permanently. The consequences of having the wrong 
tissues producing the products of inserted genes could be 
disastrous. 35 

Finally, as in gene therapy on somatic cells, introducing 
foreign DNA into the zygote may affect the regulation of the 
cell in some undetermined way. Embryological development 
depends on a precise set of genetic instructions; disruption of 
this process is therefore much more likely to have serious 
adverse consequences than a disruption of the regulatory 
mechanisms operating in a subset of somatic cells. Instead of 
being therapeutic, therapy on zygotes or on more-developed 
embryos might be teratogenic and increase the incidence of 
congenital abnormalities. 

In addition to the technical uncertainties involved, genetic 
manipulation of embryos raises serious ethical concerns. 
Altering the human gene pool by eliminating "bad" traits is a 
form of eugenics, about which there is strong concern. In 1982, 
the Council of Europe requested "explicit recognition in the 
European Human Rights Convention of the right to a genetic 
inheritance which has not been interfered with, except in 
accordance with certain principles which are recognized as 
being fully compatible with respect for human rights." 36 



33 Ralph L. Brinster et aL, Somatic Expression of Herpes Thymidine 
Kinase in Mice Following Injection of a Fusion Gene into Eggs, 27 
Cell 223 (1981). 

34 Richard D. Palmiter et aL, Differential Regulation of Metallothion- 
ein — Thymidine Kinase Fusion Genes in Transgenic Mice and Their 
Offspring, 29 Cell 701 (1982). 

35 Bob Williamson, Reintroduction of Genetically Transformed Bone 
Marrow Cells into Mice, 284 Nature 397 (1980). 

36 Council of Europe Parliamentary Assembly, 23rd Ordinary Session, 
Recommendation 934, Strasbourg (1982). 



48 



Splicing Life: Chapter 2 



Yet the meaning of "respect for human rights" is vague. 
Some favor gene therapy in embryos because it offers a 
treatment other than abortion for genetic defects. But — espe- 
cially in the early years while techniques are being perfected — 
it would probably be standard practice to examine the genetic 
and cytologic "health" of any embryos and either not to 
implant or, if already implanted, to abort any found to be 
abnormal. Not to do so would risk creating offspring who have 
genetic problems created by the "therapy" rather than natural- 
ly occurring defects. 37 

Furthermore, unless the presence or absence of a genetic 
defect could be established at a very early stage without 
harm — that is, at or just prior to fertilization or in a 2 to 4 cell 
zygote — it would be difficult to determine to whom gene 
therapy ought to be applied. Yet without such a determination, 
the use of gene splicing as a "treatment" seems dubious. In 
most cases identified by genetic screening, both parents are 
carriers of a recessive condition (those who have only a single 
defective gene of a pair and do not manifest the disease); in 
such cases, there is only a 25% chance that the disease is 
present in any zygote. It would not seem appropriate to run the 
risk of zygote therapy when three out of four of the potential 
"patients" do not need treatment. 

Therefore, the technical uncertainties, the ethical implica- 
tions, and the low probability of actually treating an affected 
person are strong contraindications against therapy of ferti- 
lized eggs or embryos becoming a useful clinical option in the 
near future. 

Genes or Genies? 

Biotechnology has made rapid advances in the past 
decade and will most likely continue to be a rapidly unfolding 
field. The awesome power entailed in these developments can 
be likened to the genie being let out of the bottle. As one 
observer of the field has noted: 

Some thirty-five years ago physicists learned how to 
manipulate the forces in the nucleus of the atom, and the 
world has been struggling to cope with the results of that 
discovery ever since. The ability to penetrate the 
nucleus of the living cell, to rearrange and transplant the 
nucleic acids that constitute the genetic material of all 
forms of life, seems a more beneficient power but one 
that is likely to prove at least as profound in its 
consequences. 38 



37 Paul Ramsey, Fabricated Man, Yale Univ. Press, New Haven, Conn. 
(1970) at 75-97. 

38 Nicholas Wade, The Ultimate Experiment, Walker and Company, 
New York (1977) at 2. 



A New Scientific Era 



49 



Stopping any enterprise out of a fear of potential evil not only 
deprives humanity of the fruits of new findings but also stifles 
strong impulses for innovation and change. Nevertheless, the 
technological allure of gene splicing ought not to be allowed to 
blind society to the need for sober judgments, publicly arrived 
at, about whether there are instances in which the price of 
going ahead with an experiment or an innovation will be higher 
than that paid by stopping the work. 39 In the next two chapters, 
the Commission examines the issues raised by gene splicing — 
particularly when used in human therapy — and the mechan- 
isms for monitoring this field. 



39 As Chief Justice Burger observed, some of the arguments presented 
against issuance of a patent for the oil-eating bacteria "remind us that, 
at times, human ingenuity seems unable to control fully the forces it 
creates — that with Hamlet, it is sometimes better 'to bear those ills we 
have than fly to others that we know not of.' " Diamond v. Chakrabar- 
ty, 447 U.S. 303, 316 (1980). 



Social and 
Ethical Issues 



The preceding chapters have described the potential 
benefits of gene splicing, but they have also suggested the 
awesome and sometimes troubling implications that have 
shared this technology's spotlight. In this chapter, the Commis- 
sion considers the social and ethical issues raised as society 
seeks ways to realize the benefits without incurring unaccept- 
able risks. The Commission has found no ethical precepts that 
would preclude the initial clinical uses of gene splicing now 
being undertaken or planned or that would categorically 
prohibit the research procedures through which knowledge is 
currently being sought in this important field. But more distant 
possibilities — either in themselves or in conjunction with other 
scientific and social developments they may foster — could 
have less benign effects. Consequently, this Report recom- 
mends steps that can and should be taken to keep the social 
and ethical implications of gene splicing before the public and 
policymakers as these developments become feasible in the 
years ahead. 

The Commission also believes, for several reasons, that 
balancing both present and future benefits and risks requires 
more than a simple arithmetical calculation. First, assessing 
this new technology through cost/benefit or risk/benefit analy- 
sis is complex because decisionmaking about gene splicing 
technology is characterized by several types and levels of 
uncertainty. The risks and benefits are poorly conceptualized 
and understood. Before they can be compared, they must be 
more clearly distinguished and articulated. Moreover, in many 
cases consensus — social or scientific — is lacking about wheth- 
er a particular outcome is in fact a benefit or a detriment. For 
example, some people regard the prospect of eliminating a 
genetic disorder in future generations as laudable, while others 
worry about the unforeseeable consequences of making alter- 



52 



Splicing Life: Chapter 3 



ations in germ-line cells. Second, while some people focus on 
particular consequences of various applications of genetic 
engineering technology, others are concerned about the accept- 
ability of genetic manipulation per se. In this context, balanc- 
ing risks against benefits makes little sense because actions, 
not consequences, are at issue. 

In the first part of this chapter, the Commission considers 
theological and secular attitudes toward the technology as 
such, rather than toward its possible consequences, and 
attempts to clarify the nature of these concerns. The Commis- 
sion then turns to an examination of the types of risks at issue. 
Although the focus is on spelling out the meaning and 
significance of certain risks, the benefits being sought through 
genetic manipulations — and those foregone if progress is 
thwarted — are also part of the equation. 

It should be emphasized that this discussion does not limit 
itself to concerns about gene splicing that the scientific 
community or the Commissioners view as valid. Moreover, this 
chapter is not a comprehensive survey of the social and ethical 
issues in genetic engineering. Since this Report addresses 
primarily the potential human uses of gene splicing, there is, for 
example, no detailed treatment of the subject of laboratory or 
industrial "biohazards" (that is, the danger of microorganisms 
to those involved in their creation or manufacture, or to the 
general public should they escape from a controlled environ- 
ment). The problems of laboratory hazards and occupational 
safety have been scrutinized for almost a decade by the United 
States Congress (through hearings and through studies by the 
Office of Technology Assessment and the Library of Congress), 
by RAC, by various bodies at the Federal, state, and local 
level, and by numerous scientific organizations. 1 

Some of the doubts about the new technology may appear 
on close examination to be overly speculative or even fanciful. 
Nonetheless, they have been forcefully expressed in the 
popular press, by religious writers, and by members of the 
general public, and they represent important concerns about 
the responsible exercise of what may prove to be the means by 
which people achieve freedom from some of the dictates of 
their genetic inheritance. 

The Commission believes it is important for society to 
address these concerns head-on. If some of these fears prove 



1 Office of Technology Assessment, U.S. Congress, Impacts of Applied 
Genetics — Micro-Organisms, Plants, and Animals, U.S. Government 
Printing Office, Washington (1981); Congressional Research Service, 
Library of Congress, Genetic Engineering, Human Genetics, and Cell 
Biology — Evolution of Technological Issues, Report Prepared for 
the Subcomm. on Science, Research and Tech. of the House Comm. on 
Science and Tech., U.S. Government Printing Office, Washington 
(1976). See also Chapter One supra, text accompanying notes 7-15. 



Social and Ethical Issues 



53 



groundless, the clearing away of spurious issues will make it 
easier to focus on any problems of real concern. Without 
necessarily resolving the problems, the Commission tries to go 
beyond clarification of the issues to recommend concrete steps 
for dealing with them. 

Concerns About "Playing God" 

Hardly a popular article has been written about the social 
and ethical implications of genetic engineering that does not 
suggest a link between "God-like powers" and the ability to 
manipulate the basic material of life. Indeed, a popular book 
about gene splicing is entitled Who Should Play God? 2 , and in 
their June 1980 letter to the President, the three religious 
leaders sounded a tocsin against the lack of a governmental 
policy concerning "[t]hose who would play God" through 
genetic engineering. 3 

Religious Viewpoints. The Commission asked the General 
Secretaries of the three religious organizations to elaborate on 
any uniquely theological considerations underlying their con- 
cern about gene splicing in humans. The scholars appointed by 
the organizations to address this question were asked to draw 
specifically on their particular religious tradition to explain the 
basis of concerns about genetic engineering; further commen- 
tary was provided by other religious scholars. 4 

In the view of the theologians, contemporary develop- 
ments in molecular biology raise issues of responsibility rather 
than being matters to be prohibited because they usurp powers 
that human beings should not possess. The Biblical religions 
teach that human beings are, in some sense, co-creators with 
the Supreme Creator. 5 Thus, as interpreted for the Commission 
by their representatives, these major religious faiths respect 
and encourage the enhancement of knowledge about nature, as 
well as responsible use of that knowledge. 6 Endorsement of 
genetic engineering, which is praised for its potential to 



2 Ted Howard and Jeremy Rifkin, Who Should Play God?, Dell 
Publishing Co., Inc, New York (1977). 

3 See Appendix B, pp. 95-96 infra. 

4 See Appendix D, pp. 107-10 infra, for a list of the religious 
commentators. 

5 Seymour Siegel, Genetic Engineering, in Proc of the Rabbinical 
Assembly of America, New York (1978) at 164. 

6 In the Biblical tradition of the major Western religions, the universe 
and all that exists in it is God's creation. In pagan religion, the gods 
inhabit nature, which is thus seen as sacrosanct, but the Biblical God 
transcends nature. However, since God created the world, it has 
meaning and purpose. God has placed a special being on earth — 
humans — formed in the image of God and endowed with creative 
powers of intelligence and freedom. Human beings must accept 
responsibility for the effects brought about by the use of the great 



54 



Splicing Life: Chapter 3 



improve the human estate, is linked with the recognition that 
the misuse of human freedom creates evil and that human 
knowledge and power can result in harm. 

While religious leaders present theological bases for their 
concerns, essentially the same concerns have been raised — 
sometimes in slightly different words — by many thoughtful 
secular observers of contemporary science and technology. 
Concerns over unintended effects, over the morality of genetic 
manipulation in all its forms, and over the social and political 
consequences of new technologies are shared by religious and 
secular commentators. The examination of the various specific 
concerns need not be limited, therefore, to the religious format 
in which some of the issues have been raised. 

Fully Understanding the Machinery of Life. Although it 
does not have a specific religious meaning, the objection to 
scientists "playing God" is assumed to be self-explanatory. On 
closer examination, however, it appears to the Commission 
that it conveys several rather different ideas, some describing 
the power of gene splicing itself and some relating merely to its 
consequences. 

At its heart, the term represents a reaction to the 
realization that human beings are on the threshold of under- 
standing how the fundamental machinery of life works. 7 A full 
understanding of what are now great mysteries, and the 
powers inherent in that understanding, would be so awesome 
as to justify the description "God-like." In this view, playing 
God is not actually an objection to the research but an 
expression of a sense of awe — and concern. 

Since the Enlightenment, Western societies have exalted 
the search for greater knowledge, while recognizing its awe- 
some implications. Some scientific discoveries reverberate 
with particular force because they not only open new avenues 
of research but also challenge people's entire understanding of 
the world and their place in it. Current discoveries in gene 
splicing — like the new knowledge associated with Copernicus 
and Darwin — further dethrone human beings as the unique 
center of the universe. By identifying DNA and learning how to 
manipulate it, science seems to have reduced people to a set of 
malleable molecules that can be interchanged with those of 
species that people regard as inferior. Yet unlike the earlier 



powers with which they have been endowed — for the betterment of 

the world — to uncover nature's secrets. 

7 As science journalist Nicholas Wade has observed: 

We are about to enter an explosive phase of discovery in which 
we are going to reach close to the great goal of Western inquiry: 
the complete understanding of man as a physical-chemical 
system. 

NOVA, Life: Patent Pending, WGBH Transcripts, Boston (1982) at 24. 



Social and Ethical Issues 



55 




revolutionary discoveries, those in molecular biology are not 
merely descriptions; they give scientists vast powers for action. 



Arrogant Interference with Nature. By what standards are 
people to guide the exercise of this awesome new freedom if 
they want to act responsibly? In this context, the charge that 
human beings are playing God can mean that in "creating new 
life forms" scientists are abusing their learning by interfering 
with nature. 

But in one sense all human activity that produces changes 
that otherwise would not have occurred interferes with nature. 
Medical activities as routine as the prescription of eyeglasses 
for myopia or as dramatic as the repair or replacement of a 
damaged heart are in this sense "unnatural." In another sense, 
human activity cannot interfere with nature — in the sense of 
contravening it — since all human activities, including gene 
splicing, proceed according to the scientific laws that describe 
natural processes. Ironically, to believe that "playing God" in 
this sense is even possible would itself be hubris according to 
some religious thought, which maintains that only God can 
interfere with the descriptive laws of nature (that is, perform 
miracles). 

If, instead, what is meant is that gene splicing technology 
interferes with nature in the sense that it violates God's 
prescriptive natural law or goes against God's purposes as they 
are manifested in the natural order, then some reason must be 



56 



Splicing Life: Chapter 3 



given 'for this judgment. None of the scholars appointed to 
report their views by the three religious bodies that urged the 
Commission to undertake this study suggested that either 
natural reason or revelation imply that gene splicing technolo- 
gy as such is "unnatural" in this prescriptive sense. Although 
each scholar expressed concern over particular applications of 
gene splicing technology, they all also emphasized that human 
beings have not merely the right but the duty to employ their 
God-given powers to harness nature for human benefit. To turn 
away from gene splicing, which may provide a means of curing 
hereditary diseases, would itself raise serious ethical prob- 
lems. 8 

Creating New Life Forms. If "creating new life forms" is 
simply producing organisms with novel characteristics, then 
human beings create new life forms frequently and have done 
so since they first learned to cultivate new characteristics in 
plants and breed new traits in animals. Presumably the idea is 
that gene splicing creates new life forms, rather than merely 
modifying old ones, because it "breaches species barriers" by 
combining DNA from different species — groups of organisms 
that cannot mate to produce fertile offspring. 

Genetic engineering is not the first exercise of humanity's 
ability to create new life forms through nonsexual reproduc- 
tion. The creation of hybrid plants seems no more or no less 
natural than the development of a new strain of E. coli bacteria 
through gene splicing. Further, genetic engineering cannot 
accurately be called unique in that it involves the creation of 
new life forms through processes that do not occur in nature 
without human intervention. As described in Chapter Two, 
scientists have found that the transfer of DNA between 



8 Pope John Paul II, who had earlier been critical of genetic engineer- 
ing, recently told a convocation on biological experimentation of the 
Pontifical Academy of Science of his approval and support for gene 
splicing when its aim is to "ameliorate the conditions of those who are 
affected by chromosomic diseases" because this offers "hope for the 
great number of people affected by those maladies." 

I have no reason to be apprehensive for those experiments in 
biology that are performed by scientists who, like you, have a 
profound respect for the human person, since I am sure that 
they will contribute to the integral well-being of man. On the 
other hand, I condemn, in the most explicit and formal way, 
experimental manipulations of the human embryo, since the 
human being, from conception to death, cannot be exploited for 
any purpose whatsoever.... I praise those who have endeav- 
oured to establish, with full respect for man's dignity and 
freedom, guidelines and limits for experiments concerning man. 
Pope John Paul II, La sperimentozione in biologia deve contribuire ol 
bene integrate deli'uomo, L'Osservatore Romano, Rome, Oct. 24, 
1982, at 2. 



Social and Ethical Issues 



57 



organisms of different species occurs in nature without human 
intervention. Yet, as one eminent scientist in the field has 
pointed out, it would be unwarranted to assume that a 
dramatic increase in the frequency of such transfers through 
human intervention is not problematic simply because DNA 
transfer sometimes occurs naturally. 9 

In the absence of specific religious prohibitions, either 
revealed or derived by rational argument from religious 
premises, it is difficult to see why "breaching species barriers" 
as such is irreligious or otherwise objectionable. In fact, the 
very notion that there are barriers that must be breached 
prejudges the issue. The question is simply whether there is 
something intrinsically wrong with intentionally crossing spe- 
cies lines. Once the question is posed in this way the answer 
must be negative — unless one is willing to condemn the 
production of tangelos by hybridizing tangerines and grape- 
fruits or the production of mules by the mating of asses with 
horses. 

There may nonetheless be two distinct sources of concern 
about crossing species lines that deserve serious consideration. 
First, gene splicing affords the possibility of creating hybrids 
that can reproduce themselves (unlike mules, which are 
sterile). So the possibility of self-perpetuating "mistakes" adds 
a new dimension of concern, although here again, the point is 
not that crossing species lines is inherently wrong, but that it 
may have undesirable consequences and that these conse- 
quences may multiply beyond human control. As noted, the 
Commission's focus on the human applications of gene splicing 
has meant that it does not here address this important set of 
concerns, which lay behind the original self-imposed moratori- 
um on certain categories of gene splicing research and which 
have been, and continue to be, addressed through various 
scientific and public mechanisms, such as RAC. 10 

Second, there is the issue of whether particular crossings 
of species — especially the mixing of human and nonhuman 
genes — might not be illicit. The moral revulsion at the creation 
of human-animal hybrids may be traced in part to the 
prohibition against sexual relations between human beings 
and lower animals. Sexual relations with lower animals are 



9 Robert L. Sinsheimer, Genetic Research: The Importance of Maxi- 
mum Safety and Forethought (Letter), N.Y. Times, May 30, 1977, at A- 
14. 

10 Despite the great attention paid to the "biohazards" of the research 
with, and products of, gene splicing, the Environmental Impact 
Statement filed by NIH on its RAC guidelines focuses on the health 
effects on humans, plants, and animals and does not deal with 
ecosystems as entities. Subsequently, however, the Environmental 
Protection Agency has supported research on the effects of introduc- 
ing recombinant organisms on the stability of various ecosystems. 



58 



Splicing Life: Chapter 3 



thought to degrade human beings and insult their God-given 
dignity as the highest of God's creatures. But unease at the 
prospect of human-animal hybrids goes beyond sexual prohibi- 
tions. 

The possibility of creating such hybrids calls into question 
basic assumptions about the relationship of human beings to 
other living things. For example, those who believe that the 
current treatment of animals — in experimentation, food pro- 
duction, and sport — is morally suspect would not be alone in 
being troubled by the prospect of exploitive or insensitive 
treatment of creatures that possess even more human-like 
qualities than chimpanzees or porpoises do. Could genetic 
engineering be used to develop a group of virtual slaves — 
partly human, partly lower animal — to do people's bidding? 
Paradoxically, the very characteristics that would make such 
creatures more valuable than any existing animals (that is, 
their heightened cognitive powers and sensibilities) would also 
make the moral propriety of their subservient role more 
problematic. Dispassionate appraisal of the long history of 
gratuitous destruction and suffering that humanity has visited 
upon the other inhabitants of the earth indicates that such 
concerns should not be dismissed as fanciful. 

Accordingly, the objection to the creation of new life forms 
by crossing species lines (whether through gene splicing or 
otherwise) reflects the concern that human beings lack the 
God-like knowledge and wisdom required for the exercise of 
these God-like powers. Specifically, people worry that inter- 
specific hybrids that are partially human in their genetic 
makeup will be like Dr. Frankenstein's monster. A striking 
lesson of the Frankenstein story is the uncontrollability and 
uncertainty of the consequences of human interferences with 
the natural order. Like the tale of the Sorcerer's apprentice or 
the myth of the golem created from lifeless dust by the 16th 
century rabbi, Loew of Prague, the story of Dr. Frankenstein's 
monster serves as a reminder of the difficulty of restoring order 
if a creation intended to be helpful proves harmful instead. 
Indeed, each of these tales conveys a painful irony: in seeking 
to extend their control over the world, people may lessen it. 
The artifices they create to do their bidding may rebound 
destructively against them — the slave may become the master. 

Suggesting that someone lacks sufficient knowledge or 
wisdom to engage in an activity the person knows how to 
perform thus means that the individual has insufficient knowl- 
edge of the consequences of that activity or insufficient 
wisdom to cope with those consequences. But if this is the 
rational kernel of the admonition against playing God, then the 
use of gene splicing technology is not claimed to be wrong as 
such but wrong because of its potential consequences. Under- 
stood in this way, the slogan that crossing species barriers is 



Social and Ethical Issues 



59 



playing God does not end the debate, but it does make a point 
of fundamental importance. 11 It emphasizes that any realistic 
assessment of the potential consequences of the new technolo- 
gy must be founded upon a sober recognition of human 
fallibility and ignorance. At bottom, the warning not to play 
God is closely related to the Socratic injunction "know 
thyself: in this case, acknowledge the limits of understanding 
and prediction, rather than assuming that people can foresee 
all the consequences of their actions or plan adequately for 
every eventuality. 12 

Any further examination of the notion that the hybridiza- 
tion of species, at least when one of the species is human, is 
intrinsically wrong (and not merely wrong as a consequence of 
what is done with the hybrids) involves elaboration of two 
points. First, what characteristics are uniquely human, setting 
humanity apart from all other species? And second, does the 
wrong lie in bestowing some but not all of these characteristics 
on the new creation or does it stem from depriving the being 
that might otherwise have arisen from the human genetic 
material of the opportunity to have a totally human makeup? 
The Commission believes that these are important issues 
deserving of serious study. 

It should be kept in mind, however, that the information 
available to the Commission suggests that the ability to create 
interspecific hybrids of the sort that would present intrinsic 
moral and religious concerns will not be available in the 
foreseeable future. The research currently being done on 



11 [WJhat made the Gallilean and the other major scientific 
revolutions disturbing is the reductionism, that we become less 
than what we are. [T]hat is what is so uncertain about gene 
therapy, because it gets back to a very fundamental ques- 
tion. . ."Is there anything unique about humans?" 

And if there isn't anything unique about humans, there's 
nothing wrong with doing gene manipulation. But if there is 
something unique about humans, then it is wrong to pass over 
the barrier, wherever the barrier is — but we don't know where 
the barrier is. 

But as soon as you ask, "Where is the barrier?" you ask, "Is 
there a barrier?" And that's frightening. If there's nothing 
unique about humans — that's not a theological question but a 
very real one. 

Testimony of Dr. French Anderson, transcript of 22nd meeting of the 
President's Commission (July 10, 1982) at 115-16. 

12 As one physician-scientist has remarked, "We must all get used to 
the idea that biomedical technology makes possible many things we 
should never do." Leon Kass, The New Biology: What Price Reducing 
Man's Estate?, 174 Science 779 (1971). See also, Ethical issues in 
experiments with hybrids of different species, Appendix I, in Church 
and Society Office, Manipulating Life, World Council of Churches, 
Geneva (1982) at 28. 



60 



Splicing Life: Chapter 3 




experimentation with recombinant DNA techniques through 
the use of single human genes (for example, the insertion of a 
particular human hemoglobin gene into mouse cells at the 
embryonic stage) or the study of cellular development through 
the combining of human genetic material with that of other 
species in a way that does not result in a mature organism (for 
example, in vitro fusion of human and mouse cells) does not, in 
the Commission's view, raise problems of an improper 
"breaching of the barriers." 

Concerns About Consequences 

To appreciate the complexity of the problem of assessing 
potential consequences and the individual and societal ability 
to cope with them, the several types of uncertainty discussed 
in Chapter One must be considered: the occurrence uncertainty 
that arises when it is not known whether a particular event 
will take place (or what sort of future it will take place in), the 
ethical uncertainty that follows from not knowing whether 
certain uses of a technology should be regarded as beneficial 
or harmful, and the conceptual uncertainty that attends new 
developments that challenge people's fundamental beliefs. The 
presence of any of these types of uncertainty complicates the 
task of estimating whether the potential benefits of genetic 
engineering outweigh the potential risks. 

What Are the Likely Outcomes? 

Medical applications. Two broad applications may be 
distinguished: the use of drugs produced by gene splicing (such 



Social and Ethical Issues 



61 



as interferon or insulin) and the direct application of gene 
splicing to human beings through gene therapy or gene surgery. 

The problems of personal safety involved in using drugs 
produced by gene splicing techniques do not appear to be 
radically different from those that accompany conventionally 
produced drugs. The basic scientific and ethical issues in this 
broad area are well known and need not be rehearsed here. 
The appropriate divisions within the Department of Health and 
Human Services (in particular, the relevant institutes of the 
NIH and the Office for Protection from Research Risks, 
regarding Federally supported research, and the Food and Drug 
Administration, regarding all drug and vaccine research) need 
to consider how to apply to genetically engineered drugs the 
existing mechanisms related to the margin of acceptable risk, 
the extent and type of animal and human studies required, the 
standards for manufacturers, and the decision to allow serious- 
ly ill patients to opt for more dangerous or less well tested 
experimental drugs. 13 According to the Department, appropri- 
ate steps are already being taken, especially by FDA, to 
resolve these issues, and the first product of gene splicing has 
already been approved. 14 

Some direct therapeutic applications of gene splicing 
technologies to human beings may present distinctive prob- 
lems of uncertainty not ordinarily encountered in more conven- 
tional medical practice. Concern has been expressed that 
serious harm might result, for example, from a malfunctioning 
gene inserted by gene therapy. Yet even here the ethical and 
policy issues do not seem appreciably different from those 
involved in the development of any new diagnostic and 
therapeutic techniques. However, in the case of genetic 
interventions that involve alteration of germ cells, especially 
stringent animal testing and other precautions are appropriate, 
since any physicial harms produced might extend to the 
subject's progeny. 

Most experts agree there is a very small likelihood that 
inheritable changes in germ cells would inadvertently occur 
when the genetic material of somatic cells is being manipulat- 
ed. However, the same animal tests and refinements of 
theoretical models that should precede the use of gene surgery 
in human beings may shed further light on whether such 
changes might produce inheritable changes in characteristic 
functions and whether they will influence germ cells. In both 



13 If there is any special concern in the evaluation of the products of 
gene splicing, it is only that in the initial stages of any new process 
there are uncertainties about some effects of the process. For example, 
bacterial contaminants are a unique by-product of gene splicing and in 
testing human insulin it was important to determine whether these 
contaminants induced deleterious antibodies in humans. 

14 See note 10, Chapter Two supra, and accompanying text. 



62 



Splicing Life: Chapter 3 



cases, the resolution of uncertainty depends upon increased 
understanding of how an inserted gene will perform its 
function. 

Subjects of gene therapy or gene surgery might suffer 
psychological as well as physical harm. The revelation that a 
person has a genetic defect or is genetically predisposed to a 
disease may produce anxiety, fear, or loss of self-esteem — 
feelings that may be intensified by the belief that the defect is a 
part of a person's constitution, rather than an outside influ- 
ence. Similarly, patients might regard alterations of their genes 
as a more profound change than a surgical procedure or the 
ingestion of a drug. Experience with genetic screening and 
counseling suggests that the special significance of a genetic 
condition to the individual may be accompanied by social 
stigma based on ignorance, but that efforts to educate individu- 
al patients and their families as well as the general public can 
minimize this problem. 15 

Evolutionary impact on human beings. Some critics warn 
against the dangers of attempting to control or interfere with 
the "wisdom of evolution" in order to satisfy scientific 
curiosity. 16 Those who hold this view object in particular to 
crossing species lines by gene splicing because they believe 
that the pervasive inability of different species to produce 
fertile offspring by sexual reproduction must be an adapative 
feature, that is, it must confer some significant survival 
advantage. Thus they view species lines as natural protective 
barriers that human beings may circumvent only at their peril, 
although the harm such barriers are supposed to shield people 
from remains unspecified. 

Most proponents of genetic engineering argue that the 
benefits it will bring are more tangible and important and will 
affect more people than those objecting suggest. Further, the 
notion of the "wisdom of evolution" that apparently underlies 
this consequentialist version of the objection to crossing 
species lines is not well founded. As the scientific theory of 
evolution does not postulate a plan that the process of 
evolution is to achieve, evolutionary changes cannot be said to 
promote such a plan, wisely or unwisely. Moreover, evolution- 
ary theory recognizes (and natural history confirms) that a 
"wise" adaptation at one time or place can become a lethal 



15 President's Commission for the Study of Ethical Problems in 
Medicine and Biomedical and Behavioral Research, Screening and 
Counseling for Genetic Conditions, U.S. Government Printing Office, 
Washington (1983). 

16 "Have we the right to counteract, irreversibly, the evolutionary 
wisdom of millions of years, in order to satisfy the curiosity of a few 
scientists? The future will curse us for it." Liebe F. Cavalieri, New 
Strains of Life— Or Death, N.Y. Times, Aug. 22, 1976 (Magazine), at 8, 
68 (quoting Erwin Chargaff). 



Social and Ethical Issues 



63 



flaw when circumstances change. So even if it could be shown 
that species barriers have thus far played an important 
adaptive role, it would not follow that this will continue. An 
evolutionary explanation of any inherited characteristic can at 
most show that having that characteristic gave an organism's 
ancestors some advantage in enabling them to live long enough 
to reproduce and that the characteristic has not yet proved 
maladaptive for the offspring. 

Furthermore, as a philosopher concerned with assessing 
the risks of genetic engineering has recently noted, the ability 
to manipulate genes, both within and across species lines, may 
become a crucial asset for survival. 

There may... come a time when, because of natural or 
man-induced climatic change, the capacity to alter 
quickly the genetic composition of agricultural plants 
will be required to forestall catastrophic famine. 17 

The consequentialist version of the warning against cross- 
ing species lines seems, then, to be no more a conclusive 
argument against genetic engineering than the admonition that 
to cross species lines is wrong because it is playing God. But it 
does serve the vital purpose of urging that, so far as this is 
possible, the evolutionary effects of any interventions are 
taken into account. 

One effect that is of particular concern to some observers 
is the loss of "heterozygote advantage" — the strength (in terms 
of individual health and species survival) engendered when 
members of a species have a variety of gene variants rather 
than all having the same gene. This advantage has two aspects. 
The first is the protection that varied genes offer for survival of 
a species in case of a radical change in environment or, more 
particularly, the occurrence of a novel pathogen. Of course, it 
would be virtually impossible to know which particular rare 
gene variant would prove to be valuable under such circum- 
stances. This consideration would favor preserving as much 
genetic variation as possible, but it would be difficult to weigh 
this against the benefit to offspring of the variant gene in its 
homozygous form. 

The second aspect is the advantage that may be conferred 
by a particular gene in past (and present) environments, 
perhaps accounting for its prevalence in a population. Al- 
though the existence of such an advantage could be construed 
as an argument against making inheritable gene changes, very 
little is actually known about the existence and nature of such 
advantages for most genes. The only instance that is widely 
acknowledged is the advantage, in terms of longevity and 



17 Stephen Stitch, The Recombinant DNA Debate, 7 Phil. & Pub. Aff. 
187 (1978). 



64 



Splicing Life: Chapter 3 



reproduction, possessed by sickle-cell carriers in tropical 
regions where malaria has been endemic. 18 

The possible beneficial effects of most gene variants are 
typically too small to be detected by current research meth- 
ods — that is, other genetic and environmental effects on the 
health, longevity, and reproductive history of a population 
make it difficult to detect whether a particular gene confers 
any advantage on those who possess it. If it becomes feasible 
to remove an apparently deleterious gene from a population 
through routine use of gene surgery, the possible loss of 
heterozygote advantage will deserve careful evaluation. 19 
Population geneticists tend to regard the loss of even minute 
advantages as serious, since such advantages can confer 
marked benefits on a species over a great many generations. 
Medical geneticists, on the other hand, are much less bothered 
by such losses because they believe that it should be possible 
to make up, through environmental manipulation (including 
medical treatment) for the loss of any advantage provided by a 
variant in any probable future environment. 

Will Benefit or Harm Occur? 

Parental rights and responsibilities. Current attitudes 
toward human reproductive activity are founded, in part, on 
several important assumptions, among them that becoming a 
parent requires a willingness, within very broad limits, to 
accept the child a woman gives birth to, that parents' basic 
duties to children are more or less clear and settled, and that 
reproduction and parenting are and should remain largely 
private and autonomous spheres of people's lives. The doors 
that genetic engineering can open challenge all three of these 
assumptions. 

Genetic counseling and screening have already undercut 
the first assumption by enabling parents to make an informed 
decision to prevent the occurrence of some genetic defects by 
terminating pregnancy, by artificial insemination, or by avoid- 
ing conception. If gene therapy or gene surgery become 
available, parents could have more control over their chil- 
dren's characteristics. They will no longer face the stark 
alternatives of either playing the hand their child has been 



18 See pp. 39-40 supra. Carriers of recessive diseases are people who 
possess one normal and one variant gene; they usually show no 
deleterious effects and may, as in the case of sickle-cell, have an 
advantage. The sickle-cell advantage is, however, dependent on time 
and place. In a temperate, nonmalarial area, or in a tropical climate 
from which the malaria parasite has been eliminated, carrying the 
sickle-cell gene would not confer an advantage. 

19 A.M. Capron, The Law of Genetic Therapy, in Michael P. Hamilton, 
ed., The New Genetics and the Future of Man, William B. Eerdmans 
Pub. Co., Grand Rapids, Mich. (1972) at 133, 140 (raising question of a 
need for a living "genes savings bank"). 



Social and Ethical Issues 



65 



dealt by the "natural lottery" or avoiding birth or conception. 
Instead, they could prevent some genetic defects through gene 
surgery on the zygote and remedy others through gene therapy 
before the genetic defect produces irreversible changes in the 
child. 

With this increased ability to act for the well-being of the 
child would come an expansion of parental responsibility. The 
boundaries of this responsibility — and hence people's concep- 
tion of what it is to be a good parent — may shift rapidly. It 
seems safe to say that one important duty of a parent is to 
prevent or ameliorate serious defects (if it can be done safely) 
and that the duty to enhance favorable characteristics is less 
stringent and clear. Yet the new technological capabilities may 
change people's view of what counts as a defect. For example, 
if what is now regarded as the normal development of 
important cognitive skills could be significantly augmented by 
genetic engineering, then today's "normal" level might be 
considered deficient tomorrow. Thus ethical uncertainty about 
the scope of a parent's obligation is linked to conceptual 
uncertainty about what counts as a defect. 

The problem of shifting conceptions of parental responsi- 
bility becomes even more complicated when the effects of 
parents' present actions on descendants beyond their immedi- 
ate offspring are considered. Deciding whether to engineer a 
profound change in an expected or newborn child is difficult 
enough; if the change is inheritable, the burden of responsibili- 
ty could be truly awesome. 

Gene splicing technology may also change people's sense 
of family and kinship. On the one hand, the possibility of 
promoting significant inheritable changes through gene surgery 
may encourage people to think of their family as extending 
further into the future than they now do. On the other hand, 
knowing that future generations may employ an even more 
advanced technology to alter or replace the characteristics 
passed on to them may weaken people's sense of genetic 
continuity. 

Traditional views of family and kinship associate repro- 
duction with genetic contribution. If genetic engineering makes 
use of reproductive technologies such as artificial insemination 
and in vitro fertilization, it will increase the strains on this 
concept of lineage. Whether or not they are accurate, people's 
beliefs that they are linked to other members of their family by 
constitutional similarities may play an important role in a 
family's sense of solidarity and group identity. Knowledge that 
the genetic link between parents and children is only partial or 
nonexistent could attenuate these feelings of kinship and 
family and the sense of continuity and support that they foster. 
Experience with adoption illustrates successful integration of 
family members who are not biologically linked, but also 



66 



Splicing Life: Chapter 3 



demonstrates the importance some individuals place on an 
association with biological parents. Here, too, there may be as 
much uncertainty about whether such changes would be 
beneficial or harmful as there is about whether they are likely 
to occur. 

Societal obligations. The concept of society's obligation to 
protect or enhance the health of children and future genera- 
tions often rests on some notion of an adequate minimum of 
health care. This benchmark, in turn, depends upon assump- 
tions about what counts as a serious defect or disability, on the 
one hand, and what constitutes normal functioning or adequate 
health, on the other. As technological capabilities grow, the 
boundary between these criteria will blur and shift, and with 
this will come changes in people's views about what society 
owes to children and to future generations. 

As new technological capabilities raise the standard of 
normal functioning or adequate health, the scarcity of societal 
resources may raise anew a very difficult question that 
theorists of distributive justice have strongly disagreed about: 
where does justice to future generations end and generosity 
begin? This question is of vital practical import, for the 
demands of justice are characteristically thought of as valid 
claims or entitlements to be enforced by the coercive power of 
the state, while generosity is usually regarded as a private 
virtue. 

Yet society has traditionally been reluctant to interfere 
with reproductive choice, at least in the case of competent 
adults. Even with the advent of genetic counseling and 
screening, social policy has for the most part scrupulously 
avoided restricting reproductive choice, either as a matter of 
justice or on any other grounds. 20 So long as the only 
alternatives are termination of pregnancy or avoidance of 
conception, any attempt to enforce a public policy designed to 
prevent genetic defects constitutes a severe infringement on 
freedom of reproductive choice. If genetic engineering and 
related reproductive technologies enable a marked reduction 
of genetic defects and the burden they impose on their victims 
and on societal resources, however, mandatory genetic treat- 
ments may be advocated. Involuntary blood transfusions of 
pregnant women have been ordered by courts when physicians 
conclude this is necessary to prevent serious harm to fetuses. 
Future developments in gene surgery or gene therapy may lead 
to further departures from the principle that a competent adult 
may always refuse medical procedures in nonemergency 
situations and from the assumption that parenting and repro- 
duction are largely private and autonomous activities. 



20 Screening and Counseling for Genetic Conditions, supra note 15, 
at second section of Chapter Two. 



Social and Ethical Issues 



67 



The commitment to equality of opportunity. Since the 
application of the burgeoning recombinant DNA technology 
will bring benefits as well as costs and since it will be funded 
at least in part by public resources, it is essential to ask several 
questions. Who will benefit from the new technology? And will 
the benefits and costs be distributed equitably? 21 Indeed, what 
sort of distribution would count as "fair" when the very thing 
that is being distributed (such as cognitive ability) is itself 
often the basis for distributing other things of value in 
society? 22 

The possibilities presented by gene therapy and gene 
surgery may in fact call into question the scope and limits of a 
central element of democratic political theory and practice: the 
commitment to equality of opportunity. One root idea behind 
the modern concept of equality of opportunity is the belief that 
because the social assets a person is born with are in no way 
earned or merited, it is unfair for someone's luck in the "social 
lottery" to determine that person's most basic prospects in life. 
Until recently, those who have sought to ground the commit- 
ment to equality of opportunity on this belief have only urged 
that social institutions be designed so as to minimize or 



21 More specifically, it is important to ask whether the further 
development of gene splicing will reinforce or perhaps exacerbate 
existing social, cultural, and economic inequalities. This factor 
explains part of the concern that has been expressed about who will 
control this technology. Although objections have focused on corpora- 
tions controlling access (through trade secrets and patents), Howard 
and Rifkin, supra note 2, at 189-207, the greatest abuses of genetics 
have involved governmental decisionmaking. Kenneth M. Ludmerer, 
Genetics and American Society: A Historical Appraisal, Johns 
Hopkins Univ. Press, Baltimore (1972) at 121-34. 

22 Suppose, for example, a society distributes certain scarce 
resources on the basis of merit — e.g., intelligence, diligence, 
physical abilities. What if intelligence could be engineered 
upward? Who would merit this increase in merit? The very 
oddity of the inquiry calls into question the continued use of 
intelligence as a basis for resolving competing claims — say, for 
admission to educational institutions or for access to the 
intelligence-raising technology itself. We could resort to the 
other coexisting merit attributes— unless they too were altera- 
ble by design. Under these conditions, how could we retain our 
system of merit distribution? If we could not, how would we 
then distribute the resources? By resort to a standard of 
efficiency? By leaving matters to a market? Or by designing a 
lottery? 

Michael H. Shapiro, Introduction to the Issue: Some Dilemmas of 
Biotechnology Research, 51 S. Cal. L. Rev.. 987, 1001-02 (1978) 
(citations omitted). 



68 



Splicing Life: Chapter 3 



compensate for the influence that the "social lottery" exerts on 
a person's opportunities. 23 Genetic engineering raises the 
question of whether equality of opportunity requires interven- 
tion in the "natural lottery" as well, for people's initial genetic 
assets, like their initial social assets, are unearned and yet 
exert a profound influence on opportunities in life. Even to ask 
this question challenges a fundamental assumption about the 
scope of principles of distributive justice, namely that they deal 
only with inequalities in social goods and play no role in 
regulating natural inequalities. 

Genetic malleability and the sense of personal identity. 
The manipulation of genes that play an important role in 
regulating processes of growth and aging or that contribute 
significantly to personality or intelligence — if it ever becomes 
possible — could have considerable impact on the way people 
think of themselves. The current tendency is to think of a 
person as an individual of a certain character and personality 
that, following the normal stages of physical, social, and 
psychological development, is relatively fixed within certain 
parameters. But this concept — and the sense of predictability 
and stability in interpersonal relations that it confers — could 
quickly become outmoded if people use gene splicing to make 
basic changes in themselves over the course of a lifetime. 
People can already be changed profoundly through psychosur- 
gery, behavior modification, or the therapeutic use of psy- 
choactive drugs. But genetic engineering might possibly pro- 
vide quicker, more selective, and easier means. Here again, 
uncertainty about possible shifts in some of people's most 
basic concepts brings with it evaluative and ethical uncertain- 
ty because the concepts in question are intimately tied to 
values and ethical assumptions. It is not likely that anything so 
profound as a change in the notion of personal identity or of 
normal stages of development over a lifetime is something to 
which people would have clear value responses in advance. 

Changing the meaning of being human. Some geneticists 
have seen in their field the possibility of benefit through 
improving human traits. 24 Human beings have the chance to 



23 John Rawls, A Theory of Justice, Harvard Univ. Press, Cambridge, 
Mass. (1973) at 83. 

24 Herman J. Muller is the scientist most associated with this view. In 
the mid-1960s he viewed selective breeding as a method for "a much 
greater, speedier, and more significant improvement of the popula- 
tion" than any direct rearrangement of genetic material possible in the 
21st century. He advocated giving women "germinal choice" through 
artificial insemination of them with the genes for superior traits. 
Herman J. Muller, Means and Aims in Human Genetic Betterment, in 
T.M. Sonneborn, ed., Control of Human Heredity and Evolution, 
Macmillan Co., New York (1965) at 100. The list of the traits found 
desirable by Professor Muller changed dramatically over time, as did 
the types of individuals whose sperm should be used — Lenin appeared 



Social and Ethical Issues 



69 



"rise above [their] nature" for "the first time in all time," as one 
leader in the field has observed: 

It has long been apparent that you and I do not enter this 
world as unformed clay compliant to any mold. Rather, 
we have in our beginnings some bent of mind, some 
shade of character. The origin of this structure — of the 
fiber in this clay — was for centuries mysteri- 
ous.... Today... we know to look within. We seek not in 
the stars but in our genes for the herald of our fate. 25 

Will gene splicing actually make possible such changes in 
"human nature" for the first time? In some ways this question 
is unanswerable since there is great disagreement about which 
particular characteristics make up "human nature." For some 
people, the concept encompasses those characteristics that are 
uniquely human. Yet most human genes are actually found in 
other mammals as well; moreover, recent work by ethologists 
and other biologists on animal behavior and capacities is 
demonstrating that many characteristics once regarded as 
unique to human beings are actually shared by other animals, 
particularly by the higher primates, although an ability to 
record and study the past and to plan beyond the immediate 
future appears to be a singularly human trait. 

Other people regard the critical qualities as those natural 
characteristics that are common to all human beings, or at least 
all who fall within a certain "normal range." "Natural" here 
means characteristics that people are born with as opposed to 
those that result from social convention, education, or accultur- 
ation. 

To consider whether gene splicing would allow the 
changing of human nature thus breaks down into two ques- 
tions. Which characteristics found in all human beings are 
inborn or have a large inborn basis? And will gene splicing 
techniques be able to alter or replace some of the genetic bases 
of those characteristics? As to the first, the history of religious, 
philosophical, and scientific thought abounds with fundamen- 
tal disputes over human nature. Without a consensus on that 



on the first list but disappeared during the Cold War. Garland E. 
Allen, Science and Society in the Eugenic Thought of H.J. Muller, 20 
Bioscience 346 (1970). 

25 Robert L. Sinsheimer, The Prospect of Designed Genetic Change, 32 
Engineering and Science 8, 13 (April 1969). Prof. Sinsheimer took a 
different view from Prof. Muller. He contrasted the "older eugenics" of 
breeding, which would require a "massive social program," with the 
new eugenics that could permit "conversion of all the unfit to the 
highest genetic level" and "could, at least in principle, be implemented 
on a quite individual basis, in one generation, and subject to no 
existing social restrictions." Id. Prof. Sinsheimer subsequently became 
very doubtful about the wisdom of changing genes. See note 19, 
Chapter One supra. 



70 



Splicing Life: Chapter 3 



issue the second question could only be answered affirmative- 
ly if it were clear that gene splicing will eventually allow the 
alteration of all natural characteristics of human beings. 

As it is by no means certain that it will ever be possible to 
change the genetic basis of all natural characteristics, it seems 
premature to assume that gene splicing will enable changes in 
human nature. At most, it can perhaps be said that this 
technology may eventually allow some aspects of what it 
means to be human to be changed. Yet even that possibility 
rightly evokes profound concern and burdens everyone with an 
awesome and inescapable responsibility — either to develop 
and employ this capability for the good of humanity or to reject 
it in order to avoid potential undesirable consequences. 

The possibility of changing human nature must, however, 
be kept in perspective. First, within the limits imposed by 
human beings' genetic endowment, there is already consider- 
able scope by means other than gene splicing for changing 
some acquired characteristics that are distinctively human. For 
example, people's desires, values, and the way they live can be 
changed significantly through alterations in social and econom- 
ic institutions and through mass education, indoctrination, and 
various forms of behavior control. Thus, even if gene splicing 
had the power that some people are concerned about, it would 
not be unique in its ability to produce major changes in what it 
means to be human — although it would be unusual in acting on 
the inheritable foundation of thoughts and actions. If the 
technology can ever be used in this way, the heritability of the 
changes ought probably to regarded as significantly different 
from any changes now possible. 26 

Second, according to the theory of evolution, the genetic 
basis of what is distinctively human continually changes 
through the interplay of random mutation and natural selec- 
tion. The concern, then, is that gene splicing will for the first 



26 If any one age really attains, by eugenics and scientific 
education, the power to make its descendants what it pleases, 
all men who live after it are patients of that power. They are 
weaker, not stronger: for though we may have put wonderful 
machines in their hands we have pre-ordained how they are to 
use them.... The real picture is that of one dominant age... which 
resists all previous ages most successfully and dominates all 
subsequent ages most irresistibly, and thus is the real master of 
the human species. But even within this master generation 
(itself an infinitesimal minority of the species) the power will be 
exercised by a minority smaller still. Man's conquest of Nature, 
if the dreams of the scientific planners are realized, means the 
rule of a few hundreds of men over billions upon billions of 
men. 

C.S. Lewis, The Abolition of Man, Collier-Macmillan, New York 
(1965) at 70-71. 



Social and Ethical Issues 



71 



time allow deliberate, selective, and rapid alterations to be 
made in the human genetic constitution. 

Finally, concern about changing human nature may at 
bottom be still more narrowly focused upon those characteris- 
tics of human beings — whether unique to the species or not — 
that are especially valued or cherished. Here, too, there may be 
disagreement as to which characteristics are most valuable 
and the value of a given characteristic may depend upon the 
social or natural environment in which it is manifested. 

In sum, the question of whether gene splicing will enable 
changes in human nature — and the ethical, social, and philo- 
sophical significance of such changes — cannot be determined 
until much more is known about human genetics, specifically 
the exact contribution of heredity to many human physical 
and, more important, behavioral traits. Indeed, one of the most 
important contributions genetic engineering could make to the 
science of behavioral genetics may be that it will help resolve 
the age-old controversy of nature versus nurture. If designed 
changes were possible, society would have to confront wheth- 
er such changes should be made, and, if they should, which 
ones. The problems created by uncertainty are particularly 
notable here since any decision about what characteristics are 
"desirable" would depend on the world that people will be 
living in, which is itself unknowable in advance. 

Unacceptable uses of gene splicing. A recent National 
Science Foundation survey indicates that though Americans 
are generally against restrictions on scientific research, "a 
notable exception was the opposition to scientists creating 
new life forms." The survey notes that 

Almost two thirds of the public believe that studies in 
this area should not be pursued. Fear of the unknown 
and of possible misuse of the discoveries by some 
malevolent dictator are among the reasons that could be 
given for opposition to such genetic engineering. 27 

Given the excesses of the eugenics movement in the 
United States and elsewhere in the early decades of this 
century and the role of eugenic theory in mass atrocities 
perpetrated by the Nazis, these fears cannot be dismissed as 
groundless. Some comfort may be drawn from the fact that 
although the possibility of directing human inheritance through 
simple breeding techniques has existed for centuries, it has not, 
with relatively minor exceptions, been attempted. Furthermore, 
the peculiar social and political circumstances that led to these 
attempts to control human reproduction through the coercive 



27 John Walsh, Public Attitude Toward Science Is Yes, but-, 215 
Science 270 (1982) (quoting National Science Foundation, Science 
Indicators 1980). 



72 



Splicing Life: Chapter 3 



power of the state are not present in this country and are 
unlikely to occur in the foreseeable future. 

Reassuring though they are, these answers are far from 
conclusive. Government control of sexual reproduction on a 
broad scale — through an enforced scheme for mating human 
beings — would require enormous repressive power and social 
control over individuals over an extended period of time. What 
might prove more tempting to a dictator or authoritarian ruling 
elite is the possibility of scientists rapidly making major 
changes in the genetic composition of a small group in the 
privacy of the laboratory. 

Though there appears at present to be no evidence that the 
government of this or any other country is attempting to use 
gene splicing for unacceptable political purposes, the Commis- 
sion believes that the appropriate posture for the public and 
the scientific community is one of vigilance. The best safe- 
guards against such abuses are a continued support of 
democratic institutions and a commitment to individual rights 
combined with public education about the actual and potential 
uses of gene splicing technology. Of course, such efforts in this 
country would not avoid undesirable uses of genetic engineer- 
ing by totalitarian governments, unless they led to effective 
international restrictions. 28 

A more subtle danger is that if genetically engineered 
changes ever become relatively easy to make, there may be a 
tendency to identify what are in fact social problems as genetic 
deficiences of individuals or to assume that the appropriate 
solution to a given problem, whether social or individual, is 
genetic manipulation. 29 The relative ease of genetic methods (if 



28 Another misuse of gene splicing with international ramifications, 
described by the World Council of Churches as a "grave hazard," is 
"the deliberate production of pathogenic micro-organisms for biologi- 
cal warfare or terrorism." Paul Abrecht, ed., 2 Faith and Science in an 
Unjust World: Report of the World Council of Churches' 
Conference on Faith, Science and the Future, Fortress Press, 
Philadelphia (1980) at 53. 

29 "In discussing the use of any science, including genetics, to solve 
social problems, it. . .becomes important to demarcate clearly the limit 
that scientific technique may be expected to contribute to an effective 
solution." Ludmerer, supra note 21, at 180. To take an extreme 
example, in a society in which gene surgery was widely used and 
accepted, it might be tempting to "solve" the problem of racial 
discrimination by making genetic changes to eliminate dark skin. A 
less fanciful example would be the decision to make genetic alter- 
ations in certain groups of workers who are exposed to dangerous 
chemicals in the workplace rather than to eliminate the dangers. 

Moreover, genetic research may denigrate the value that 
society has perceived in the moral and autonomous aspects of 
human conduct by forcing society to question the limits of free 



Social and Ethical Issues 



73 



gene therapy becomes an accepted medical technique) should 
most certainly not draw attention away from the underlying 
social causes of such problems. 

Distributing the power to control gene splicing. Beyond 
any fear of the malevolent use of gene splicing, attention must 
be paid to a more basic question about the distribution of 
power: who should decide which lines of genetic engineering 
research ought to be pursued and which applications of the 
technology ought to be promoted? 

This question is not ordinarily raised about medical 
technology in general. When it is, the assumption is that for the 
most part the key decisions are to be made by the relevant 
experts, the research community, and the medical profession, 
guided by the availability of research funds (which come 
predominately from Federal agencies) and by the dictates of 
medical malpractice law and of state and Federal regulatory 
agencies designed to protect the public from very tangible, 
unambiguous harms. Yet genetic engineering is more than a 
new medical technology. Its potential uses, as discussed, 
extend far beyond intervention to cure or prevent disease or to 
restore functioning. This more expansive nature makes it 
unlikely that decisions about the development of gene splicing 
technology can be made appropriately within institutions that 
have evolved to control medical technology and the practice of 
medicine. 

Clearly, adequate institutional arrangements for decision- 
making about the further development of gene splicing technol- 
ogy must assign a substantial role to experts in the field. Yet it 
is important to understand the unavoidable limitations of 
technical expertise. On the one hand, there are the limitations 
of the experts' knowledge; on the other, there are the limita- 
tions of technical knowledge itself, no matter how thorough. 
Experts in genetic engineering can provide the most accurate 
available data, from which probability statements can be 
formulated. But neither geneticists nor scientists experienced 
in risk assessment have any special expertise about evaluative 
and conceptual uncertainties. An expert might conclude that 
there is a 5% probability that a certain harmful outcome will 
occur, but that knowledge is not sufficient for deciding whether 
such a probability is an acceptable degree of risk. Nor can 
scientific expertise answer the question of whether the bur- 
dens of risk would fall disproportionately upon some people, 



will and self-determination. Thus, genetic research has the 

power to reorder society's priorities and restructure its values; 

fundamentally, it can change the structures of human thought 

and the social construction of reality. 
Marc Lappe and Patricia Archbold Martin, The Place of the Public in 
the Conduct of Science, 52 S. Cal. L. Rev. 1535, 1537 (1978) (citations 
omitted). 



74 



Splicing Life: Chapter 3 



for this is a moral, not a scientific, question. This is not to say, 
of course, that scientific experts should not make moral 
judgments or that if they do they ought to be ignored. But the 
limitations of expertise must be clearly understood. 

In general the public can reasonably rely on the judgments 
of experts in the field to the extent that at least three 
conditions are satisfied: (1) there is a strong consensus among 
the experts, (2) the process by which individuals come to be 
identified as experts is not unduly influenced by political 
factors or other forces unrelated to their qualifications as 
experts, and (3) the experts are not subject to serious conflicts 
of interest that are likely to distort their judgments or to make 
their advice unreliable. 30 Whether, or to what extent, these 
conditions are satisfied cannot be answered once and for all. 
Instead, they must be viewed as useful rules-of-thumb for 
assessing and reassessing the role of experts in the formation 
of responsible public policy. 

Commercial-academic relations. Concern over the latter 
two points — unacceptable uses of the technology and the 
power of control it — have contributed to a growing public 
debate about the increased commercial involvement with 
university-based research on gene splicing. Constraints on 
support for basic science research by the Federal government 
in the past decade have been compounded by economic 
problems that have reduced both state budgets for higher 
education and the grants of philanthropic foundations. Conse- 
quently, academic research scientists are turning increasingly 
to industry, 31 forming ties that have raised concern about how 
to accommodate the divergent goals and norms of science and 
industry. 

Universities have historically been dedicated to increasing 
the general fund of knowledge through basic research, the open 
exchange of information and ideas, and the training of new 
researchers and scholars. These goals may run headlong into 
those of industry — the development of marketable products 
and techniques through applied research by maintaining a 
competitive posture, protecting trade secrets, and seeking 
patent protection. 



30 See Stitch, supra note 17. 

31 Estimates have put industry support of academic research at about 
$200 million per year. Although this represents only about 4% of what 
government contributes, it is a growing proportion. The formation in 
the past decade of about 200 new private ventures to pursue research 
and development in genetic engineering has been paralleled by 
increased interest on the part of existing industrial firms in universi- 
ties that have strong programs in molecular biology. This interest has 
been capped by several well publicized multimillion dollar agree- 
ments. 



Social and Ethical Issues 



75 









IW-vu ^n/€jf} 


f 'A 





The conflicts occasioned by these developments are not 
unique to genetic engineering; indeed, at the beginning of this 
century a number of expanding universities shifted their focus 
from the traditional arts and sciences as they became allied 
with the burgeoning electrical and chemical industries. Medi- 
cine, agriculture, econometrics, solid state physics, and com- 
puter science have all been advanced in part because of 
combined forces of industry and universities. Yet the recent 
similar developments in biotechnology present these issues in 
sharper relief for several reasons. 

First, commercialization of biotechnology seems to be 
proceeding more rapidly than in chemistry and physics. And in 
gene splicing, the gap between theory and application — be- 
tween a graduate student's work in the lab and a highly 
lucrative product — is often quite small. Finally, the range of 
potential applications of the research is very broad. 

Increased private funding for bioengineering research has 
therefore sparked questions about conflicts of interest and 
about the impact of commercialization on academe more 
generally. 32 Some see these issues as private concerns relating 
only to the particular universities and firms contracting with 
each other, a view reflected at a recent conference at Pajaro 
Dunes when university officials and industry representatives 



32 That journey of discovery can only be undertaken once, and 
it would be better undertaken by people who have no interest 
in anything other than discovering the truth, whose hands are 
clean, whose motives can never be criticized. That's in the 
public's interest; that is in science's true interest. And if the 
commercialization, if this secondary goal of getting rich, ever 
starts to influence a scientist's primary goal, a university's 
primary goal of discovering the truth, then the scientists 
themselves, I hope, will have the sense to put a halt to it. 
Wade, supra note 7, at 24-25. 



76 



Splicing Life: Chapter 3 



met in private to discuss concerns about commercialization. 
The participants at this privately funded conference of 5 
leading universities and 11 corporations issued a statement 
intended to "get some general principles on the record" and 
"set an agenda for further discussion of the issues." The 
document raised questions of contract review and disclosure, 
exclusive licensure, and conflicts of interest encountered by 
university and faculty. It encouraged university faculties to 
continue examination of these issues over which commenta- 
tors have noted that "[pluralism and a certain measure of 
confusion prevail." 33 

Other issues are also at stake: Can professional virtue be 
maintained in the face of considerable financial temptations? 
How will private funding change professors' outlooks? 34 Will 
fewer be interested in teaching undergraduates? Will they 
encourage graduate students to focus on projects with maxi- 
mum commercial potential, instead of those that would foster a 
more well rounded background? Will commercialization effect 
a shift from basic to applied research and, if so, with what 
consequences? Will the secrecy required by industry impede 
the free exchange of scientific information? What about 
conflicts of interest when the same academic department 
includes owners or employees of competitive bioengineering 
ventures? Will academic appointments and promotions be 
skewed to favor those who can attract private research funds 
to the university? 

The Association of American Universities has recently 
suggested that it become a clearinghouse for information on 
commercialization. 35 These and related questions have also 
been the subject of debate in the press and before Congressio- 
nal committees. Undoubtedly, such concerns spill over into the 
public arena when the question is whether the new agreements 
are "skimming off the cream produced by decades of taxpayer 



33 Barbara J. Culliton, Paj'aro Dunes: The Search for Consensus, 216 
Science 155 (1982); Draft Statement Pajaro Dunes Conference (March 
25-27, 1982). 

34 One physician-scientist who formerly held high budgetary and 
science advisory positions in the Federal government and who is 
presently the Dean of a school of public health has suggested that the 
financial agreements between universities and medical school faculty 
in the clinical departments could be "at least partially relevant" in 
finding a means of protecting the research and educational commit- 
ments of the basic-science faculties while generating added income. 
Gilbert S. Omenn, Taking University Research into the Marketplace, 
307 New Eng. J. Med. 694, 699-700 (1982). 

35 Letter from Robert M. Rosenzweig, chairman of the Association of 
American Universities Committee on University/Industry Relations, 
to Reps. Don Fuqua and Albert Gore, Jr. (Oct. 28, 1982) (on report of 
AAU study group). 



Social and Ethical Issues 



77 



funded work," as Rep. Albert Gore, Jr., put it in opening 
Congressional hearings on the subject. 36 Only a continuing 
public debate over these as-yet-unresolved questions on the 
commercialization of biotechnology can ensure that the pub- 
lic's interests are being met — its interest in the integrity and 
credibility of scientific research, in a sound and balanced 
research agenda, and in the wise expenditure of Federal 
research dollars. 

Continuing Concerns 

A distinction has been drawn in this Report between two 
views: (1) that gene splicing technology is intrinsically wrong 
or contrary to important values and (2) that, while the 
technology is not inherently wrong, certain of its applications 
or consequences are undesirable. Regarding the latter, it has 
also been noted that genetic engineering involves an array of 
uncertainties beyond those usually found in technological 
developments. Not only is the occurrence of specific desirable 
or undesirable consequences impossible to predict but the 
application of gene splicing could have far-reaching conse- 
quences that could alter basic individual and social values. 

The Commission could find no ground for concluding that 
any current or planned forms of genetic engineering, whether 
using human or nonhuman material, are intrinsically wrong or 
irreligious per se. The Commission does not see in the rapid 
development of gene splicing the "fundamental danger" to 
world safety or to human values that concerned the leaders of 
the three religious organizations. 37 Rather, the issue that 
deserves careful thought is: by what standards, and toward 
what objectives, should the great new powers of genetic 
engineering be guided? 

Even though the many issues raised by gene splicing in 
human beings need to be considered one by one if their 
potential consequences are to be clearly assessed, it would be 
a mistake to compartmentalize the issues. 38 Although the 



36 Commercialization of Academic Biomedical Research, Hearings 
before the Subcomm. on Invest, and Oversight and the Subcomm. on 
Science, Research and Tech. of the House Comm. on Science and 
Tech., 97th Cong., 1st Sess., June 8, 1981, at 2. 

37 See Appendix B, pp. 95-96 infra. 

38 The predominant methodological strategy of biological re- 
search is reductionism: the isolation of the phenomenon under 
study from its usual circumstances, thereby reducing the 
number of variables that affect the analysis. This allows a 
clearer understanding of the "basic" processes, and has led to 
important discoveries. 

The strength of reductionism is the principle of isolation. This 
principle, however, is also inherently limiting: the circum- 



78 



Splicing Life: Chapter 3 



Commission has not found any ethical, social, or legal barriers 
to continued research in this field, there remains an important 
concern expressed by the warning against "playing God." It 
not only reminds human beings that they are only human and 
will some day have to pay if they underestimate their own 
ignorance and fallibility; it also points to the weighty and 
unusual nature of this activity, which stirs elusive fears that 
are not easily calmed. 

At this point in the development of genetic engineering no 
reasons have been found for abandoning the entire enter- 
prise — indeed, it would probably be naive to assume that it 
could be. Given the great scientific, medical, and commercial 
interest in this technology, it is doubtful that efforts to 
foreclose important lines of investigation would succeed. If, for 
example, the United States were to attempt such a step, 
researchers and investment capital would probably shift to 
other countries where such prohibitions did not exist. To 
expect humanity to turn its back on what may be one of the 
greatest technological revolutions may itself betray a failure to 
recognize the limits of individual and social self-restraint. Even 
if important lines of research in this country or elsewhere could 
be halted, to do so would be to run a different sort of risk: that 
of depriving humanity of the great benefits genetic engineering 
may bring. 

Assuming that research will continue somewhere, it seems 
more prudent to encourage its development and control under 
the sophisticated and responsive regulatory arrangements of 
this country, subject to the scrutiny of a free press and within 
the general framework of democratic institutions. In light of the 
potential benefits and risks — uncertain though they may be at 
this point — a responsible social policy on genetic engineering 
requires the cooperation of many institutions and organiza- 
tions. 



stances of the investigation are necessarily "unreal" in every- 
day terms. Of course, it may be that the isolated phenomena 
behave similarly under natural circumstances. This assump- 
tion, however, is often uncertain and may frequently be untrue. 
Moreover, the characteristics of those natural circumstances 
are rarely fully known. In some cases, knowledge of the 
multiple external influences upon biological processes could 
lead to a perception of those processes quite different from 
those obtained in the isolation of laboratory study. A critical 
understanding of present biological knowledge requires recog- 
nition of those methodological weaknesses. Public participation 
in science, by broadening the range of factors considered at 
each stage of investigation, provides a means of counteracting 
biases resulting from reductionist strategy. 
Halsted R. Holman and Diana B. Dutton, A Case for Public Participa- 
tion in Science Policy Formation and Practice, 51 S. Cal. L. Rev. 1505, 
1513-14 (1978) (citation omitted). 



Social and Ethical Issues 



79 



Efficient regulation and oversight will require considerable 
division of responsibility among different bodies and agencies. 
Legal controls will necessarily focus on the prevention of 
tangible harms to individuals and the environment. Nonethe- 
less, the Commission believes it is crucial that those entrusted 
with such oversight and regulation do not lose sight of the more 
elusive, but equally important, concerns about the human 
significance of genetic engineering or neglect such concerns 
because they do not fit neatly into existing institutional 
jurisdictions. The continued development of gene splicing 
approved in this Report will require periodic reassessment as 
greater knowledge is gained about the ethical and social, as 
well as the technical, aspects of the subject. 



Protecting 
the Future 



4 



The material presented in the earlier chapters provides the 
basis for the Commission's recommendations on the means 
through which the issues generated by genetic engineering can 
continue to receive appropriate attention. These issues are not 
matters for a single day, deserving of only occasional attention. 
They will be of concern to the people of this country — and of 
the entire globe — for the foreseeable future; indeed, the results 
of research and development in gene splicing will be one of the 
major determinants of the shape of that future. Thus, it is 
important that this field, with its profound social and ethical 
consequences, retain a place at the very center of "the 
conversation of mankind." 1 

Specifically, in the preceding material the Commission has 
seen that: 

(1) The careful attention paid by scientists, private 
groups, and government officials to the immediate 
health and environmental risks has been rewarded 
with a record of safe and fruitful research and 
development. 

(2) Although the Federal Interagency Committee on 
Recombinant DNA Research has been inactive for 
several years, the Recombinant DNA Advisory Com- 
mittee (RAC) at the National Institutes of Health 
(NIH) has provided an informal means for intragov- 
ernmental communication, as well as overseeing the 
safety of NIH-funded research. 

(3) The issues raised by the projected human uses of 
gene splicing, which heretofore have not received 



1 Michael Oakeshott, The Voice of Poetry in the Conversation of 
Mankind, in Rationalism in Politics and Other Essays, Metheun, 
London (1962) at 197. 



82 



Splicing Life: Chapter 4 



attention, are as at least as complex and important 
as those addressed by RAC thus far. 

(4) These issues would benefit from an evaluation 
process that is continuing rather than sporadic, to 
allow a review body to develop coherent standards 
and orderly procedures, while making provisions for 
unexpected developments in gene splicing and other 
changes in the world at large. 

(5) It would be desirable to develop means for such an 
evaluation process now, not because of any threat of 
imminent harm but because the issues are better 
addressed in anticipation rather than in the wake of 
a possible untoward or unforeseen outcome. 

(6) The issues are so wide-ranging as to require a 
process that is broad-based rather than primarily 
expert, since the issues cannot be resolved on 
technical grounds alone and since many of the most 
knowledgeable scientists are deeply involved in the 
field as researchers or even as entrepreneurs. 

These observations do not, of course, point to any single 
framework for a continuing oversight of this area. Because of 
its large role in funding biomedical research and its statutory 
responsibilities to ensure that environmental, industrial, and 
pharmaceutical safety standards are being met, the Federal 
government will be a participant in any well-designed process 
of planning and review. But this function need not be regarded 
as exclusively governmental. A variety of organizations in the 
private sector — such as the American Association for the 
Advancement of Science, the National Academy of Sciences, 
the Industrial Biotechnology Association, and the Pharmaceuti- 
cal Manufacturers Association — could well play important 
leadership and educational roles. 

Finally, within the governmental sector, the responsibility 
for oversight — not only coordinating what is being done but 
also identifying what still needs to be done — is very important. 
It, too, can be supplied by a variety of means, including 
Congressional committees and the Office of Technology As- 
sessment. Or the body charged with overall responsibility 
might also have direct regulatory power, as opposed to the 
authority to stimulate appropriate actions on the part of those 
agencies that do have the power. 

Objectives 

The President's Commission believes that the design of 
any oversight group should be guided by several objectives. 
First, the group should regard education as a primary responsi- 
bility. It is necessary to educate the scientific community about 



Protecting the Future 



83 




the social and ethical implications of its work as well as to 
educate the public about science. 



Second, the group should have roles both of general 
oversight and of leadership within the Federal government. For 
this, it will need direct access, through liaison arrangements, to 
all Federal departments or agencies with a large stake in 
sponsoring, regulating, or scrutinizing work in this field. At a 
minimum it should possess "action-forcing power," whereby 
departments and agencies are required to publish its regulatory 
recommendations for comment in the Federal Register within a 
specified time and then either to adopt or reject the recommen- 
dations, with an explanation likewise published in the Federal 
Register. 

Third, the body should be capable of leading, as well as 
reflecting, public thinking on the important issues before it; it 
can serve as an intermediary between biomedical scientists 
and the public, helping to translate and clarify the ideas and 
concerns of each for the other. To do so, it will need diverse 
membership. 2 It also ought to conduct its work in public and 
seek to have it widely disseminated. A policymaking process 
that draws on nonscientists and avoids unnecessary secrecy is 



2 One well-known investigator has urged: "If this investigation 
[work in genetic engineering] is done with man, the study 
should be made with collaborators who can protect genetics 
from public scorn by having scientists working with articulate 
sociologists and psychologists who plan for a long time before 
doing the engineering." 
Kenneth M. Ludmerer, Genetics and American Society: A Historical 
Appraisal, Johns Hopkins Univ. Press, Baltimore (1972) at 179 (quoting 
Dr. Clarence P. Oliver). 



84 



Splicing Life: Chapter 4 



likely not only to lead to better results but also to inspire much 
greater public confidence in, and support for, research efforts 
themselves. 3 

Fourth, it should strive to operate on scientifically sound 
premises. For this it will need a means of drawing on groups of 
scientists for advice and explanation in a way that does not 
lead it to be dominated by the scientific community. 

Fifth, it should treat 1 — in as unified a framework as 
possible — all the issues raised by genetic engineering: labora- 
tory and industrial safety, environmental hazards, agricultural 
and commercial opportunities and pitfalls, international ramifi- 
cations, biomedical benefits and risks, and social and ethical 
implications. 

Sixth, insofar as possible, the oversight functions should 
be separated from any sponsoring functions, so that no 
conflicts of interest, of the sort that plagued the Atomic Energy 
Commission, will arise. 

Revising RAC 

RAC, which had been created in October 1974 as a 
scientific and technical committee, was subsequently made 
into a more representative body by HEW Secretary Joseph 
Califano, through the addition of nonscientific members of the 



3 If this industry follows the path that appears easier initially, 
the cloistered avoidance of other forces of society, it will pay a 
penalty years hence should some event force a public inquiry. 
George E. Brown, Jr., The Policymaking Challenge of the Bioengineer- 
ing Industry, 4 Recombinant DNA Technical Bull. 121, 123 (1981). 
Rep. Brown, former chairman of the House Subcommittee on Science, 
Research and Technology, has urged the commercial concerns in the 
genetic engineering field to establish public crust by forming an 
"active" and "open" industrial council to exercise powers of censure, 
laboratory approval, and similar functions. Id. at 122. 

But there needs to be a broader entity, at least initially. There 
should be a council with a broad and diverse membership to 
look at the entire range of issues that a genetic engineering 
industry raises. Scientists, lay people, lawyers, policymakers, 
regulators, clergy, and other groups should be represented in a 
council of manageable size.... There will be objections to the 
inclusion of nonscientists on the panel deciding scientific 
matters. These have been heard before but experience has 
shown that these people become valuable contributors. 

...Knowing the aversion that researchers have to being bur- 
dened by broad social and ethical considerations, I would 
understand a reluctance by researchers to willingly submit to 
what would undoubtedly be a time consuming discussion. But 
these views will be present in any public debate and are better 
incorporated sooner than later. 
Id. at 123. 



Protecting the Future 



85 



public. Recently, Dr. Donald Fredrickson, who presided over 
the transformation as the Director of NIH, suggested that the 
time for a "third generation" RAC may have arrived. 4 The 
President's Commission concurs, since there is plainly great 
value in building on the history — largely regarded as success- 
ful — of RAC. Design of an appropriate body for the task will 
require consideration of many factors, some of which (such as 
funding) are beyond the purview of the President's Commis- 
sion. 5 But as a starting point, it may be helpful if the 
Commission suggests possible formats for consideration by the 
President and Congress. 6 



4 Joseph G. Perpich, Industrial Involvement in the Development of 
NIH Recombinant DNA Research Guidelines and Related Federal 
Policies, 5 Recombinant DNA Technical Bull. 59, 77 (1982) (quoting a 
talk by Dr. Fredrickson, rDNA Controversy: The NIH Viewpoint, 
delivered at the annual meeting of the American Association for the 
Advancement of Science, Jan. 7, 1982, to be published in a volume 
edited by Raymond Zalinskas and Burke Zimmerman). 

The idea... is to make RAC more representative of both the 
scientific and regulatory communities as well as the public to 
be better equipped to deal with the emerging problems and be 
relieved of some of the detailed burden of reviewing minor 
administrative concerns. Such a "third generation" RAC should 
be accountable to a Cabinet officer. . . 

The concept was instantly adopted, at least in principle, by Dr. 

Ray Thorton, chairman of RAC and a fellow panelist at AAAS. 
"Third Generation" of RAC Suggested by Dr. Fredrickson, 2 Genetic 
Engineering Letter 1 (1982). 

5 In Diamond v. Chakrabarty, 447 U.S. 303 (1980), the Supreme Court 
reached a similar conclusion about the competence of the judiciary to 
decide, within the context of a patent case, the merits of the 
contention of the Federal government and various amici curiae that 
genetic engineering presented "grave risks" of "pollution and di- 
sease,... loss of genetic diversity, and... depreciation of] the value of 
human life." The Court found that deciding whether the research "may 
pose a serious threat to the human race" or that such concerns were 
"fantasies generated by fear of the unknown" was a matter for 
Congress and the Executive. 

The choice we are urged to make is a matter of high policy for 
resolution within the legislative process after the kind of 
investigation, examination, and study that legislative bodies 
can provide and courts cannot. That process involves the 
balancing of competing values and interests, which in our 
democratic system is the business of elected representatives. 
Id. at 317. The Commission has tried to advance the process of 
"investigation, examination, and study" but the ultimate "balancing of 
competing values and interests" is for elected officials. 

6 These suggestions draw on the work of the Federal Interagency 
Committee on Recombinant DNA Research, which was created at the 
direction of President Ford in 1976. That Committee recommended the 
adoption of legislation explicitly to regulate recombinant DNA re- 
search, in light of the disjointed fashion in which existing legislation 



86 



Splicing Life: Chapter 4 



One means of supplementing RAC, now that it is less 
active since the laboratory biohazards are no longer regarded 
as urgent matters, would be through a mixed public-private 
sector body established outside the Federal government. 7 This 
format has been employed in the initial work in other fields 
and there are plainly many organizations, ranging from those 
with academic and commercial interests to the religious bodies 
that prompted the present study, from which such a group 
could draw. 

If it is felt that the extent of Federal responsibility is so 
great, both for safety and for promotion of this field, that a 
governmental body of greater breadth than the present RAC is 
needed, the Interagency Committee established in 1976, which 
has been inactive for the past several years, could be 
reinvigorated. 8 This would have the advantage of direct 
involvement of the leading Federal agencies but the disadvan- 
tage that its membership is entirely governmental and its 
meetings are not subject to the Federal Advisory Committees 
Act. 

Rather than creating additions to RAC, it might be 
preferable to redesign it. The greater scope of work for the new 
RAC would have two aspects. First, the range of issues must 
certainly be broadened beyond laboratory and manufacturing 
hazards. Second, the involvement of other Federal bodies must 
be greater. Placing the successor to RAC outside of any one 



touched on the field. President Carter endorsed the resulting legisla- 
tion, which was drafted by the Department of Health, Education and 
Welfare. It was introduced in Congress by Senator Edward M. 
Kennedy and Representative Paul G. Rogers. As redrafted by his 
health subcommittee after hearings, Senator Kennedy's bill called for 
the creation of an 11-member Presidential Commission (with 5 
scientific and 6 lay members); the House version would have created 
a 15-person advisory committee to the Secretary of HEW. 

7 Corporate lawyer Milton Wessel has argued for the value, as a 
general matter, of institutions involved with science and technology 
pursuing a "rule of reason" in place of the adversary approach to the 
country's emerging socioscientific problems. If the private sector does 
not take the lead in resolving these emotion-laden issues in a fashion 
that serves the public interest, he believes the public will demand 
much greater direct governmental control. Milton R. Wessel, Science 
and Conscience, Columbia Univ. Press, New York (1980). 

8 Dr. Fredrickson, who approves of the location of RAC within NIH as 
the governmental body with clearest responsibilities in the field, has 
also praised the interagency group: 

In addition to maintaining a desirable amount of ecumenical 
spirit within the federal bureaucracy, [it] had the virtue of being 
there and ready for immediate convocation in the event one of 
the hypothetical hazards materialized and national resources 
needed to be mobilized and coordinated. 
Supra note 4, at manuscript p. 9. 



Protecting the Future 



87 



department should promote this end, without making it merely 
a group of Federal agency representatives. 9 

One format would be the creation of a Genetic Engineering 
Commission (GEC) of 11 to 15 members from outside the 
government that would meet regularly to deal solely with this 
field. This group could have a majority of nonscientists — 
members of the general public as well as experts in ethics and 
philosophy, law, the social and behavioral sciences, and public 
and private management. In addition to a small staff, the GEC 
could have a series of Technical Panels that could provide 
expertise in (1) laboratory research; (2) agricultural and 
environmental uses and dangers; (3) manufacturing concerns; 
(4) human uses; and (5) international controls. It should also be 
able to draw on a panel of liaison officers from the Depart- 
ments of Agriculture, Commerce, Defense, Energy, Health and 
Human Services (one each from the Centers for Disease 
Control, the National Institutes of Health, the Food and Drug 
Administration, and the National Institute for Occupational 
Safety and Health), Interior, Labor (including one from the 
Occupational Safety and Health Administration), and State; 
the National Science Foundation; the National Endowment for 
the Humanities; and the Environmental Protection Agency. 

An alternative format would be to assign responsibility for 
oversight of genetic engineering to the body that succeeds the 
President's Commission. 10 This arrangement could have some 
advantages. Principally, it would permit the continuing over- 
sight of gene splicing to be integrated into the consideration 
given to the social, legal, and ethical implications of other 
important developments in the biomedical arena. Also, it 
would recognize that the flow of work for such a body is not 
always at an even pace; a group with a more diverse mandate, 
such as the President's Commission, could turn its attention to 
other areas rather than wasting time when there are no gene 
splicing issues needing attention, while still being ready should 
such issues need prompt attention. 



9 The experience of the Federal Interagency Committee is instructive. 
That committee was created as a result of Congressional pressure. It 
was very active during its first year, when it was responding to a 
mandate from the highest levels of the Executive Branch to review the 
nature and scope of recombinant DNA activities in the Federal and 
private sectors and to recommend appropriate responses in terms of 
guidelines, regulations, and/or legislation. Once this task was com- 
plete, the committee slowly slid into quiescence, not because DNA 
research no longer raised important issues, but because the member 
agencies (other than NIH) were not active in this field so the 
committee did not have much to "coordinate." 

10 A two-year extension of the Commission is proposed in pending 
legislation, S.2311, the Biomedical Research, Training, and Medical 
Library Assistance Amendments of 1982. 



88 



Splicing Life: Chapter 4 



Giving the assignment to the present Commission's succes- 
sor might have several disadvantages, however. First, it seems 
unlikely that there will be any paucity of items to consider; in 
addition to the work presently performed by RAC, the agenda 
of any new body would be augmented by the many issues that 
RAC has felt were beyond its mandate. Second, not all the 
issues are ones of "bioethics," and assigning the task to the 
President's Commission might narrow the range of issues to be 
considered. (For example, in the present study, the Commis- 
sion did not feel it had a basis for making judgments on the 
issues of patents and trade secrets, although they are impor- 
tant questions for the future of genetic engineering.) Third, by 
focusing primarily on genetic engineering, a GEC would be 
better able to develop among its members and staff the 
necessary familiarity with all the major issues and the 
underlying science. 

Whatever mechanism is adopted, from among these or 
others, the quality and diversity of the members appointed to 
such a body, as well as the processes through which it 
deliberates, will be central determinants of its success. Wheth- 
er the body is given formal regulatory powers, or merely the 
authority to issue guidelines and give advice, its major impact 
will rest on its ability to educate and to persuade. It must set its 
sights high if it is to function as "an agency for the protection of 
the future." 11 To protect the future people must sometimes be 
willing to act with vision and spirit as well as with humility — 
and striking a balance between courage and prudence is never 
easy. 



11 Arthur Lubow, Playing God with DNA, 8 New Times 48, 64 (Jan. 7, 
1977) (quoting Robert L. Sinsheimer). 



Glossary 



A 



Amino acids - The building blocks of proteins. There are 20 
common amino acids; they are joined together in a strictly 
ordered "string" that determines the character of each protein. 

Anneal - The process by which the complementary base pairs 
in the strands of DNA combine. 

Bacteriophage (or phage) - A virus that multiplies in bacteria. 
Bacteriophage lambda is commonly used as a vector in 
recombinant DNA experiments. 

Biotechnology - The collection of industrial processes that 
involve the use of biological systems. For some of these 
industries, these processes involve the use of genetically 
engineered microorganisms. 

Cell fusion - The fusing together of two or more cells to 
become a single cell. 

Chromosomes - The threadlike components of a cell nucleus 
that are composed of DNA and protein. They contain most of 
the cell's DNA. 

Classical genetics - The body of knowledge that deals with the 
laws of inheritence of genes such as determined by appropriate 
test matings. [Compare molecular genetics.) 

Clone - A group of genetically identical ceils or organisms 
asexually descended from a common ancestor. All cells in the 
clone have the same genetic material and are exact copies of 
the original. 



90 



Splicing Life: Appendix A 



Conjugation - The one-way transfer of DNA between bacteria 
in cellular contact. 

Crossing-over - A normal genetic event that always occurs 
during the reduction division of germ cell formation, which 
involves the breakage and reunion of DNA molecules. 

Cut - A break that occurs in both strands of a DNA molecule 
opposite one another. 

Cytoplasm - The protoplasm of a cell, external to the cell's 
nuclear membrane. 

Diploid - A cell with the usual number of chromosomes, in 
contrast to haploid. 

DNA (deoxyribonucleic acid) - The genetic material found in 
all living organisms. Every inherited characteristic has its 
origin somewhere in the code of each individual's complement 
of DNA. 

DNA vector - A vehicle for transferring DNA from one cell to 
another. 

Embryo - The early developmental stage of an organism 
produced from a fertilized egg. 

Escherichia coli (E. coli) - A bacterium that commonly 
inhabits the human intestine. It is an organism used in many 
microbiological experiments. 

Endonuclease - An enzyme that nicks or cuts DNA molecules; 
unlike a exonuclease, it does not require a free end to act. (See 
also restriction enzyme.) 

Enzyme - A functional protein that catalyzes a chemical 
reaction. Enzymes control the rate of metabolic processes in an 
organism. 

Eukaryote - A higher, compartmentalized cell characterized 
by its extensive internal structure and the presence of a 
nucleus containing the DNA. All multicellular organisms are 
eukaryotic. The simpler cells, the prokaryotes, have much less 
compartmentalization and internal structure; bacteria are 
prokaryotes. 

Exonuclease - An enzyme that removes bases sequentially 
from the ends of a linear DNA molecule. 



Glossary 



91 



Fermentation - The biochemical process of converting a raw 
material such as glucose into a product such as ethanol. 

Gamete - A mature reproductive cell. 

Gene - The hereditary unit, such as a segment of DNA coding 
for a specific protein. 

Gene expression - The manifestation of the genetic material of 
an organism as specific traits. 

Gene mapping - Determining the relative locations of different 
genes on a given chromosome. 

Genetic code - The biochemical basis of heredity consisting of 
codons (base triplets along the DNA sequence) that determine 
the specific amino acid sequence in proteins and that are the 
same for all forms of life studied so far. 

Genetic drift - Changes of gene frequency in small populations 
due to chance preservation or extinction of particular genes. 

Germ cell - The sex cell (sperm or egg). It differs from other 
cells in that it contains only half the usual number of 
chromosomes. Male and female germ cells fuse during 
fertilization. 

Germ plasm - The total genetic variability available to an 
organism, represented by the pool of germ cells or seed. 

Hybridoma - A rapidly proliferating cell made by fusing a 
myeloma cell with another cell. (Myeloma is a cancer of 
plasma cells.) 

Haploid - A cell with half of the usual number of 
chromosomes. 

Hormones - The "messenger" molecules of the body that help 
coordinate the actions of various tissues; they produce a 
specific effect on the activity of cells remote from their point of 
origin. 

In vitro - Outside the living organism and in an artificial 
environment. 

In vivo - Within the living organism. 

Messenger RNA - Ribonucleic acid molecules that transmit 
the genetic information from the nucleus to the cytoplasm, 
where they guide protein synthesis. 



92 



Splicing Life: Appendix A 



Molecular genetics - Deals with the study of the nature and 
biochemisty of the genetic material. Includes the technologies 
of genetic engineering that involve the directed manipulation of 
the genetic material itself. 

Monoclonal antibodies - Antibodies derived from a single 
source or clone of cells that recognize only one kind of antigen. 

Mutation - Any change that alters the sequence of bases along 
the DNA, changing the genetic material. 

Nick - A break in one strand of a DNA molecule in which no 
bases are removed. 

Nucleic acid - A polymer composed of DNA or RNA subunits. 

Nucleotides - The fundamental units of nucleic acids. They 
consist of one of the four bases — adenine, guanine, cytosine, 
and thymine (uracil in the case of RNA) — and its attached 
sugar-phosphate group. 

Phage - [See bacteriophage.) 

Plasmid - Hereditary material that is not part of a 
chromosome. Plasmids are circular and self-replicating. 
Because they are generally small and relatively simple, they 
are used in recombinant DNA experiments as acceptors of 
foreign DNA. 

Polymorphism - A gene or unexpressed DNA variant that 
occurs in a population with a frequency too great to be 
explained by mutation. 

Protein - A linear polymer of amino acids; proteins are the 
products of gene expression and are the functional and 
structural components of cells. 

Recombinant DNA - The hybrid DNA produced by joining 
pieces of DNA from different sources. 

Restriction enyzme - An enzyme within a bacterium that 
recognizes and degrades DNA from foreign organisms, thereby 
preserving the genetic integrity of the bacterium. In 
recombinant DNA experiments, restriction enyzmes are used 
as tiny biological "scissors" to slice foreign DNA before it is 
recombined with a vector. These enzymes are also called 
restriction endonucleases. 



Glossary 



93 



RNA (ribonucleic acid) - In its three forms — messenger RNA, 
transfer RNA, and ribosomal RNA — it assists in translating the 
genetic message of DNA into the finished protein. 

"Shotgun" method - A technique for obtaining the desired 
gene that involves chopping up the entire genetic complement 
of a cell using restriction enzymes, then attaching each DNA 
fragment to a vector and transferring it into a bacterium, and 
finally screening the bacteria to locate those producing the 
desired product. 

Somatic -cell - One of the cells composing parts of the body 
[e.g., tissues, organs) other than a germ cell. 

Totipotency - Capability of a cell, prior to differentiation, to 
express all of its genetic material. 

Transduction - The process by which foreign DNA becomes 
incorporated into the genetic complement of the host cell. 

Transformation - The transfer of genetic information by DNA 
separated from the cell. 

Vector - A transmission agent; a DNA vector is a self- 
replicating DNA molecule that transfers a piece of DNA from 
one host to another. 

Virus - An infectious agent that requires a host cell in order 
for it to replicate. It is composed of either RNA or DNA 
wrapped in a protein coat. 

Zygote - A fertilized egg. 



Letter from 
Three General 
Secretaries 




June 20, 1980 



We are rapidly moving into a new era of fundamental 
danger triggered by the rapid growth of genetic engineering. 
Albeit, there may be opportunity for doing good; the very term 
suggests the danger. Who shall determine how human good is 
best served when new life forms are being engineered? Who 
shall control genetic experimentation and its results which 
could have untold implications for human survival? Who will 
benefit and who will bear any adverse consequences, directly 
or indirectly? 

These are not ordinary questions. These are moral, ethical, 
and religious questions. They deal with the fundamental nature 
of human life and the dignity and worth of the individual 
human being. 

With the Supreme Court decision allowing patents on new 
forms of life — a purpose that could not have been imagined 
when patent laws were written — it is obvious that these laws 
must be reexamined. But the issue goes far beyond patents. 

New life forms may have dramatic potential for improving 
human life, whether by curing diseases, correcting genetic 
deficiencies or swallowing oil slicks. They may also, however, 
have unforeseen ramifications, and at times the cure may be 
worse than the original problem. New chemicals that ultimate- 
ly prove to be lethal may be tightly controlled or banned, but 
we may not be able to "recall" a new life form. For unlike DDT 
or DES — both of which were in wide use before their tragic 
side effects were discovered — life forms reproduce and grow 
on their own and thus would be infinitely harder to contain. 

Control of such life forms by any individual or group poses 
a potential threat to all of humanity. History has shown us that 
there will always be those who believe it appropriate to 



96 



Splicing Life: Appendix B 



"correct" our mental and social structures by genetic means, so 
as to fit their vision of humanity. This becomes more dangerous 
when the basic tools to do so are finally at hand. Those who 
would play God will be tempted as never before. 

We also know from experience that it would be naive and 
unfair to ask private corporations to suddenly abandon the 
profit motive when it comes to genetic engineering. Private 
corporations develop and sell new products to make money, 
whether those products are automobiles or new forms of life. 
Yet when the products are new life forms, with all the risks 
entailed, shouldn't there be broader criteria than profit for 
determining their use and distribution? Given all the responsi- 
bility to God and to our fellow human beings, do we have the 
right to let experimentation and ownership of new life forms 
move ahead without public regulation? 

These issues must be explored, and they must be explored 
now. It is not enough for the commercial, scientific or medical 
communities alone to examine them; they must be examined 
by individuals and groups who represent the broader public 
interest. In the long-term interest of all humanity, our govern- 
ment must launch a thorough examination of the entire 
spectrum of issues involved in genetic engineering to determine 
before it is too late what oversight and controls are necessary. 

We believe, after careful investigation that no government 
agency or committee is currently exercising adequate oversight 
or control, nor addressing the fundamental ethical questions in 
a major way. Therefore, we intend to request that President 
Carter provide a way for representatives of a broad spectrum 
of our society to consider these matters and advise the 
government on its necessary role. 

We also intend to ask the appropriate Congressional 
Committees to begin immediately a process of revising our 
patent laws looking to revisions that are necessary to deal with 
the new questions related to patenting life forms. In addition, 
we will ask our government to collaborate with other govern- 
ments with the appropriate international bodies, such as the 
UN, to evolve international guidelines related to genetic 
engineering. 

Finally, we pledge our own efforts to examine the religious 
and ethical issues involved in genetic engineering. The reli- 
gious community must and will address these fundamental 
questions in a more urgent and organized way. 

Dr. Claire Randall, General Secretary 
National Council of Churches 

Rabbi Bernard Mandelbaum, General Secretary 
Synagogue Council of America 

Bishop Thomas Kelly, General Secretary 
United States Catholic Conference 



Federal Government 
Involvement in 
Genetic Engineering* 



Laboratory Research 

Several agencies conduct or sponsor scientific research 
that either uses recombinant DNA molecules or studies the 
technique and its applications. 

Department of Agriculture 

The Department of Agriculture (USDA) funds several 
types of research involving genetic engineering in plants, 
animals, and microorganisms. Most research is in the following 
general categories: (1) studies of the normal genetic mechan- 
isms of plants and animals (including the structure and 
function of nuclear, mitochondrial, and chloroplast genes, and 
the control of gene expression during development), with the 
goal of transferring functioning genes into higher organisms; (2) 
studies of viruses, bacteria, fungi, and other microbial agents 
that are pathogens or symbionts of plants, animals, or insects. 
The goal of the research is the eventual use of recognition 
sequences of microbes to introduce genes into higher organ- 
isms, extend the active range of nitrogen-fixing bacteria, or 
modify agents to achieve biological control of pathogenic 
microbes or insects; (3) studies to isolate and clone DNA 
sequences for useful proteins, and to gain the expression of 
these genes in bacteria in order to manufacture products, such 
as vaccines [e.g., corn, soybean, wheat) and specific enzymes; 
and (4) studies to genetically engineer microbial organisms that 
will more efficiently produce useful fermentation products 



* The information included in this Appendix was provided by govern- 
ment officials as part of a survey conducted by the President's 
Commission in September 1980 and updated in August 1982. 



98 



Splicing Life: Appendix C 



[e.g., fermented foods, antibiotics) or degrade certain com- 
pounds [e.g., industrial wastes, residual pesticides). 

Department of Defense 

The interest of the Department of Defense (DOD) and its 
subordinate military departments in the use of genetic engi- 
neering technology is principally directed to the prevention of 
disease and the fielding of those devices and methodologies 
that will ensure the survival and continued effectiveness of 
military personnel in a toxic environment. 

Current DOD programs using genetic engineering tech- 
niques include vaccines for dysentery, malaria, botulism, 
anthrax, hemorrhagic fevers (including Rift Valley and Dengue 
fevers), rickettsial diseases, and trypanosomiases — all items of 
significance to the medical protection of U.S. Forces. Studies 
continue on cloning the human gene for acetylcholinesterase 
and the receptor for acetylcholine (which will be applied in 
developing treatments for military personnel exposed to chemi- 
cal warfare agents) and on cloning the squid gene for Diisopro- 
pylfluorophosphatase for organophosphorus detoxification. 
Further studies deal with the molecular basis of marine 
biofouling. 

Department of Energy 

Many of the Department of Energy's (DOE) investigators 
have used recombinant DNA techniques in their work. Genes 
are being cloned in order to obtain sufficient material to 
analyze the structure of genes, to deduce structure-function 
relationships, to analyze the molecular basis of mutation, and 
to obtain genetic material as probes for analysis. The genes 
come from a variety of sources, but the cloning is always done 
in microorganisms. 

Continuing studies of a number of proteins are being 
expanded to include analysis of the structure of the genes 
involved. These include trytophan synthetase, metallothionein, 
rhodopsin, globin, and several enzymes involved in DNA 
repair processes. Studies are also under way to look at several 
aspects of cancer; these include cloning the genes for several 
liver enzymes that are turned off when cancer develops, 
cloning a naturally occurring mouse tumor virus, and develop- 
ing cloning and isolation techniques to search for genes that 
occur only in tumor tissues. 

In other projects, a gene from E. coli is being put in 
Chinese hamster cells to study the occurrence of mutations; an 
unusual form of DNA is being prepared by recombinant DNA 
techniques to study how it is repaired; and genes in corn are 
being cloned to understand genetic elements called transpo- 
sons. In a collaborative project with the Centers for Communi- 



Federal Government Involvement 



99 



cable Diseases, fragments of DNA from a pathogenic organism 
are being cloned so probes can be developed to identify the 
organism in human tissues. 

In projects related to biomass and fermentation, the genes 
for the multienzyme complex called cellulase are being cloned 
and analyzed, and an attempt is being made to introduce the 
enzyme xylose isomerase into certain kinds of yeast so they 
may ferment pentoses. 

Future work being considered is along much the same 
lirie— examination of structure-function relationships of genes 
of particular interest, use of cloned genes to prepare hard-to- 
isolate gene products, and applied approaches as the needs 
and opportunities arise. 

Environmental Protection Agency 

The Office of Research and Development has undertaken 
a number of research studies and has represented the agency 
in various outside forums. Two assessments of the state of 
recombinant DNA usage in agricultural and industrial sectors 
and the impact of these applications on the environment have 
been commissioned. In addition, projects now in progress deal 
with events associated with environmental release of mi- 
crobes. One study involves a computer simulation of the 
probability of escape of genomes from laboratories or commer- 
cial fermenters. Another is exploring survival of organisms in 
environmental media, and a third deals with the likelihood of 
genetical exchange of microbes in water and sewage. The 
office has participated with other groups and has established 
an institutional advisory group. Most recently, the staff initiat- 
ed a seminar series designed to acquaint policymakers with 
environmental consequences of the technology, and they will 
participate in a research conference on the genetic control of 
environmental pollutants in 1983. 

National Institutes of Health 

The National Institutes of Health (NIH) is the major funder 
of basic research involving recombinant DNA techniques. It 
also supports several projects specifically designed for risk 
assessment. Both as a funding source and as part of its 
responsibilities for the protection of human research subjects, 
NIH will have a major role in clinical trials of gene therapy. 

National Science Foundation 

The National Science Foundation (NSF) funds several 
types of biological research involving recombinant DNA 
molecules: (1) gene regulation and expression; (2) structure and 
organization of chromosomes; (3) evolution and systematics; 
(4) organization and function of subcellular bodies; (5) transfer 



100 



Splicing Life: Appendix C 



of genes including nitrogen-fixing genes to plants; and (6) 
development of recombinant DNA technology. 

Regulation 

Several agencies have regulatory authority that extends to 
products of recombinant DNA technology. 

Department of Agriculture 

USDA has responsibilities for the inspection and certifica- 
tion of some products of recombinant DNA technology and the 
regulation of some organisms that may be used for recombi- 
nant DNA research. For example, USDA regulates importation 
into the United States of the foot-and-mouth virus that is used 
in vaccine research. Like other animal biological products, this 
vaccine would be licensed by the USDA. 

USDA also establishes guidelines for the introduction and 
distribution of pathogenic microorganisms, other pests (insects, 
nematodes, noxious weeds), and plant germ plasm. 

Environmental Protection Agency 

In 1976, EPA's general counsel staff determined that some 
of the Federal statutes at EPA may apply to aspects of the 
bioengineering field. Their analysis included the Clean Air Act, 
Clean Water Act and Toxic Substances Control Act (TSCA) 
but did not address the other statutes under the Administrator. 

Although several EPA statutes may apply, none has 
initiated a program to address biotechnology issues. Staff 
involved in administering the Federal Insecticide, Fungicide 
and Rodenticide Act and TSCA are currently reviewing the 
applied genetics field to consider the impact of the technology. 
The pesticide program has made the most progress, since it has 
already carried out registration reviews of over a dozen 
microbial agents that are used as pesticides. Generic testing 
guidelines are being readied for publication that will lay out 
the product chemistry, toxicology, environmental fate, and 
effects on nontarget species for testing for demonstration of 
safety in the registration process. The extent to which the 
guidelines may be altered to evaluate genetically engineered 
microbes as contrasted with naturally occurring agents has not 
been determined. Under TSCA, the Agency has broad authori- 
ty over new and existing chemicals. The potential for TSCA to 
address the products of applied genetics as "new" chemicals is 
also being studied. 



Federal Government Involvement 101 



Federal Trade Commission 

The Federal Trade Commission's (FTC) activities, which 
involve primarily enforcement actions, are concerned with the 
prevention and elimination of unfair business practices and 
restraint of trade. The Commission may exercise its enforce- 
ment powers to protect competition and consumers against 
practices that restrict research, development, production, or 
marketing of genetic technology and products or that might 
result in harm to consumers through unfair or deceptive 
advertising and marketing practices. 

Department of Health and Human Services 

Centers for Disease Control. The Centers for Disease 
Control (CDC) has responsibility for the interstate shipment of 
etiologic [I.e., disease-inducing) agents and applies existing 
regulations (pertaining, for example, to volume and packaging) 
to DNA products identified as etiologic agents. [See also 
Department of Transportation below.) CDC provides a 24-hour 
hotline for reports of leakage of any such agents during 
transport. 

Center for Infectious Diseases. As part of its responsibili- 
ty for disease diagnosis and prevention, this Center conducts 
epidemiological investigations and research on a broad range 
of infectious diseases of public health importance. Consider- 
able emphasis is placed on studying the molecular biology of 
many pathogenic microorganisms, their epidemiology, disease- 
producing mechanisms, antibiotic-resistance profile, and the 
development of candidate vaccines. Some of the molecular 
biology research involves the use of recombinant DNA technol- 
ogy. Examples of such research are: (1) cloning pencillinase- 
producing plasmid fragments from Neisseria gonorrhoeae in E. 
Coli to test for mobilization properties, and cloning TV. gonor- 
rhoeae genes for studies of proline synthesis and to further the 
use of auxotyping as an epidemiologic tool; (2) cloning genes 
for cadmium resistance and penicillinase production, which 
appear to be linked in Staphylococcus aureus and S. epidermi- 
dis, to determine if S. epidermidis can serve as a reservoir for 
the penicillinase genes; (3) cloning of genes from influenza 
viruses, poliovirus, rabiesvirus, and variola into bacteria to (a) 
study the structure and function of nucleic acids, (b) study viral 
pathogenesis, (c) develop molecular diagnostic procedures [i.e., 
hybridization tests to identify viral agents), (d) improve and 
develop technology for use in molecular epidemiology, and (e) 
develop techniques for rapid sequencing of those peptides 
identified as the key antigenic moiety for influenza strains of 
known or anticipated epidemic potential; (4) cloning of Vene- 
zuelan equine encephalitis (VEE) virus genome into bacteria to 
enable subsequent reconstuctions of the viral genome se- 



102 



Splicing Life: Appendix C 



quence, to identify those regions that code for antigenic 
glycoproteins responsible for inducing immunity, and to recon- 
struct synthetically the amino acids required for a vaccine. 

National Institutes for Occupational Safety and Health 
(NIOSH). NIOSH has recently undertaken a program to help 
identify potential health hazards to workers involved in 
recombinant DNA work. Walk-through surveys were conduct- 
ed at six companies. Assessments of the potential for worker 
exposure were made based on process design and operations. 
NIOSH has also developed, with other CDC experts, guidelines 
for medical surveillance of exposed workers. Finally, NIOSH is 
continuing research into the best available fermentation con- 
trol technology, which would form the basis for future control 
in the use of recombinant organisms. 

Food and Drug Administration. Products under the Food 
and Drug Administration's (FDA) regulatory jurisdiction pro- 
duced using recombinant DNA methods are subject to the 
same regulatory standards as products derived from conven- 
tional technologies. 

In general, it is expected that new applications for FDA 
approval will be required for products obtained via recombiant 
DNA technology that fall under the Agency's regulatory 
purview. For the first such products, which are currently under 
clinical investigation, the requirement for new applications is 
clear: human insulin has not previously been marketed; 
recombinant human growth hormone (hGH) is actually methio- 
nyl-hGH, an analogue of the (approved) natural substance; and 
some recombinant human interferon preparations may be 
chemically different from the interferons derived directly from 
human cell sources. 

Moreover, despite substantial experience with products 
such as vaccines, antibiotics, and toxoids derived from natural 
components of microorganisms, there is little experience with 
substances produced by genetic manipulation of microorga- 
nisms. Moreover, some of the microorganisms that may be 
employed to produce recombinant products have not been 
previously employed to produce drugs or biologies for human 
use. Thus, the possibility of encountering novel toxicities is a 
concern. 

In the future, it is expected that, where consistent with 
individual Bureau policy, new applications will be required for 
products obtained via recombinant DNA technology, even if 
identity is demonstrated with the natural substance, or with a 
previously approved substance produced in a conventional 
way. However, each case will be handled on an ad hoc basis 
because of the many different kinds of products expected. Data 
required to support such applications will vary widely and 
depend on a number of factors, including, but not limited to: 
whether the product is identical to a previously approved 



Federal Government Involvement 103 



product; the projected length of time of use; the amount of 
previous experience with the product produced conventionally; 
and the amount of previous experience with recombinant 
DNA-derived substances. 

National Institutes of Health. The National Institutes of 
Health (NIH), with its Recombinant DNA Advisory Committee, 
has established guidelines for the safe conduct of recombinant 
DNA research. The guidelines have been adopted by all 
Federal agencies and apply to all Federally funded research, 
with voluntary compliance by the private sector. As part of the 
voluntary compliance scheme, NIH reviews some private 
research. A limited number of recombinant DNA experiments 
must be reviewed and approved by NIH prior to initiation. 
Biosafety committees are required at institutions that conduct 
recombinant DNA research and that are registered with NIH. 

Department of Labor 

Occupational Safety and Health Administration. The Oc- 
cupational Safety and Health Administration (OSHA) will 
continue to monitor activities in genetic engineering and collect 
information that might be used as a basis for a regulatory 
effort. OSHA has no immediate plans for regulatory activities 
in this area. 

Department of Transportation 

Etiologic agents are categorized as hazardous materials 
and are subject to DOT regulations issued under the Hazard- 
ous Materials Transportation Act (18 U.S.C. 1801 et seq.). 
These regulations are associated with CDC regulations and 
apply to the transport of recombinant DNA molecules that 
have been incorporated into any etiologic agent listed in the 
CDC regulations. 

Information /Education 

Department of Commerce 

The National Bureau of Standards has not been involved 
thus far in any work involving recombinant DNA. It expects, 
however, to carry out some of its traditional roles, such as 
establishing equivalency of chemical products and developing 
test methods and reference standards for products developed 
by recombinant DNA methods. One example might be deter- 
mining whether any feedstocks produced with recombinant 
DNA methods contain by-products not produced by traditional 
processes. The Bureau's focus is on physics, chemistry, and 
engineering. 

Until the Supreme Court reached its decision on the 
patentability of living organisms in June 1980, the Patent and 



104 



Splicing Life: Appendix C 



Trademark Office (PTO) had deferred the processing of the 
more than 100 patent applications involving products of genetic 
engineering. The PTO has now taken some form of action on all 
these applications, applying the usual standards of patentabili- 
ty. Patent applications involving use of recombinant DNA 
techniques or related technology were being received at the 
estimated rate of 10-15 per month in mid-1982. 

The Department of Commerce is also interested in the 
protection of trade secrets, should private companies come 
under Federal regulation. 

Department of State 

The Department of State's involvement in genetic engi- 
neering, recombinant DNA and related technology emanates 
from its broad mandate to pursue U.S. foreign policy objec- 
tives, and its specific statutory responsibility for coordinating 
U.S. scientific and technological collaboration with other 
nations. Foreign policy concerns of relevance to genetic 
engineering include: international trade and commerce, partic- 
ularly elimination of existing or potential nontariff trade 
barriers and the protection of patent rights; national security 
aspects of technology transfer; and environmental health and 
safety. 

Although the Department of State does not directly 
sponsor or carry out research or development in this field, it 
obtains and provides information on policies and programs of 
other nations to support the R&D efforts of U.S. public and 
private institutions. The Department also coordinates U.S. 
participation in a broadening array of international organiza- 
tions active in genetic engineering in an effort to influence the 
character of these efforts and to maximize their benefits. Such 
organizations include the World Health Organization, the UN 
Environment Program, the Economic Commission for Europe, 
and the Organization for Economic Cooperation and Develop- 
ment (OECD), as well as international nongovernmental bodies 
such as the International Council of Scientific Unions (ICSU). 

National Academy of Sciences 

The National Academy of Sciences (NAS) has not under- 
taken any activities focusing on the ethics of human applica- 
tions of genetic technology. However, it has sponsored a 
Workshop of Priorities in Biotechnology Research for Interna- 
tional Development. In addition, on May 20, 1982, a meeting 
was held of an ad hoc Committee on New Separation 
Processes for Genetic Engineering and Chemical and Energy 
Industries. A major focus of this meeting was on applications 
of biotechnology to separation processes, e.g., removal of toxic 
or valuable contaminants from liquid phases. The meeting was 



Federal Government Involvement 105 



convened by NAS's Commission on Engineering and Technical 
Systems. 

National Institutes of Health 

In 1976 the Federal Interagency Committee on Recombi- 
nant DNA Research was formed under NIH auspices. It had 
three responsibilities: (1) review the nature and scope of DNA 
activities in the Federal and private sector; (2) determine the 
feasibility of extending NIH guidelines to all sectors; and (3) 
recommend legislative or executive action concerning these 
guidelines. The group met until 1980 at which time an Industrial 
Practices Subcommittee was formed. The full Committee 
recommended that legislation be passed extending NIH's 
recombinant DNA guidelines to the private sector, but 
Congress failed to pass the measure. Neither the full Interagen- 
cy Committee nor its Industrial Practices Subcommittee is 
currently active. 

National Science Foundation 

Law and Social Sciences Program. This program supports 
a research project entitled "New Regulatory Forms: Recombi- 
nant DNA Research," which is carried out by Anselm Strauss 
at the University of California, San Francisco. As changes in 
science and technology have raised questions directly related 
to broader social, economic, political, and ethical issues, new 
law has been developed, requiring new patterns of regulation. 
This project specifically addresses issues of the scope of 
regulation, the role for technical specialists, and the criteria 
and standards applied by regulatory agencies and courts in 
terms of the history of regulation of DNA research. The study 
focuses on the relationships among interested parties in the 
regulatory arena, with attention to who those participants are 
and the "social worlds" they represent (the occupational 
settings in which they operate) and how they represent them. 
Emphasis is given to the strategy and tactics of conflict and 
negotiation among those parties. A manuscript describing this 
study is expected to be completed in early 1983. 

Ethics and Values in Science and Technology. The pro- 
gram on Ethics and Values in Science and Technology (EVIST) 
supports research that shows promise of contributing to 
professional and public understanding of the ethical and value 
implications of genetic engineering. The program has supported 
the work of Charles Weiner, at MIT, to develop a historical 
archive of public and professional controversies surrounding 
recombinant DNA research and development. In September 
1981 the NSF also awarded a grant to Clifford Grobstein, at the 
University of California, San Diego, to conduct a technology 
assessment of potential human applications of recent advances 
in genetics. Monographs are in preparation describing studies 



106 



Splicing Life: Appendix C 



by Sheldon Krimsky at Tufts University on a social history of 
the recombinant DNA controversy and by a team of research- 
ers headed by Diana Dutton at Stanford University concerning 
the roles of public participation in controversies surrounding 
medical innovations, including a discussion of recombinant 
DNA. 

Office of Technology Assessment, U.S. Congress 

The Office of Technology Assessment has undertaken 
three studies in the field of genetics: 

(1) Impacts of Applied Genetics: Micro-organisms, Plants 
and Animals: This report, released in April 1981, describes 
current and potential applications of classic and molecular 
genetic technologies to produce substances in three major 
industrial sectors — pharmaceuticals, chemicals, and food. 
Three applications involving release of genetically altered 
organisms to the environment are discussed: mineral leaching 
and recovery, enhanced oil recovery, and pollution control. 
Current and potential applications to higher plants and ani- 
mals are described. Other parts of the report address the 
problems of assessing the risk of genetic engineering, the 
regulation of the technology, the patenting of life forms, and 
various science/society issues raised by the new genetic 
techniques. Policy options for Congressional consideration are 
described as well as the pros, cons, and consequences 
associated with them. 

(2) Genetic Screening and Cytogenetic Surveillance in the 
Workplace: This assessment examines the state of the art of 
genetic screening and cytogenetic surveillance as means of 
identifying individuals at high risk for particular chemicals in 
the workplace or environments where the entire workforce 
may be at risk. It examines legal issues raised by genetic 
testing in the workplace, applicable ethical principles, and 
economic considerations. A survey of genetic testing in the 
workplace was conducted as part of the study, which is due to 
be completed in the fall of 1982. 

(3) A Comparative Assessment of the Commercial Devel- 
opment of Biotechnology: This assessment examines whether 
biotechnology (which includes recombinant DNA, cell fusion, 
fermentation, and enzyme technology) is developing in the 
United States in a way that will leave the nation in a 
competitive position with other nations in the years ahead. 
Besides describing the state of the art here and in other 
countries, major influences likely to affect future development 
of the industry are reviewed. These include government 
policies on research funding, patents, health and safety regula- 
tions, antitrust laws, and taxation as well as industrial-aca- 
demic relationships and their influence on funding, research, 
manpower, training, and information flow. The study is due to 
be completed in the summer of 1983. 



The Commission's 
Process 



Commission Hearings 

September 16, 1980 
Techniques and Problems 

Dr. Gilbert S. Omenn, Associate Director for Human 
Resources, Veterans, and Labor, Office of Management 
and Budget, Executive Office of the President 

Richard Roblin, Ph.D., Cancer Biology Program, Frederick 
Cancer Research Center, Frederick, Maryland 

Conceptual Issues 

Richard Hull, Ph.D., Associate Professor of Philosophy, 
State University of New York, Buffalo 

Federal Activity 

Dr. William Gartland, Director, Office of Recombinant 
DNA Activities, National Institutes of Health 

Michael Lambert, Professional Assistant, Technology 
Assessment and Risk Analysis, National Science 
Foundation 

Joshua Menkes, Ph.D., Technology Assessment and Risk 
Analysis Group, National Science Foundation 

Arthur Norberg, Ph.D., Program Manager, Ethics and 
Values in Science and Technology, National Science 
Foundation 

Dr. Joseph Perpich, Executive Secretary, Federal 

Interagency Advisory Committee on Recombinant DNA 
Research, National Institutes of Health 



108 



Splicing Life: Appendix D 



Dr. Bernard Talbot, Executive Secretary, Industrial 
Practices Subcommittee, National Institutes of Health 

July 10, 1982 

Panel Discussion of Draft Report 

Dr. French Anderson, Chief, Laboratory of Molecular 
Hematology, National Heart, Lung, and Blood Institute, 
National Institutes of Health 

Nicholas Wade, Editorial Board, New York Times and 
author of The Ultimate Experiment: Man-Made Evolution 

Public Comment 

J. Robert Nelson, Ph.D., Professor of Theology, Boston 
University 

Former Commissioners 

These members served on the Commission while this study 
was being conducted; their terms of service, which were 
completed before the Report was approved, are indicated in 
parentheses. 

Renee C. Fox (Aug. 1979-Jan. 1982) 
Mario Garcia-Palmieri (Aug. 1979-Aug. 1982) 
Frances K. Graham (May 1980-Jan. 1982) 
Albert R. Jonsen (Aug. 1979-Aug. 1982) 
Mathilde Krim (Nov. 1979-Dec. 1981) 
Donald N. Medearis (Aug. 1979-Jan. 1982) 
Anne A. Scitovsky (Aug. 1979-Aug. 1982) 
Carolyn A. Williams (Sept. 1980-Aug. 1982) 

Advisors to the Commission 

Special Consultant: Tabitha M. Powledge, M.S. 
Consultant Panel 

David Baltimore, Ph.D., Professor of Microbiology, 
Massachusetts Institute of Technology 

Peter Day, Ph.D., Director, Plant Breeding Institute, 
Trumpington, Cambridge, England 

Troy Duster, Ph.D., Director, Institute for the Study of 
Social Change, University of California, Berkeley 

Zsolt Harsanyi, Ph.D., Office of Technology Assessment, 
U.S. Congress 



109 



Ruth Hubbard, Ph.D., Harvard Biological Laboratories, 
Harvard University 

Peter Barton Hutt, Esq., Covington & Burling, Washington, 
D.C. 

Dr. David Jackson, Genex Laboratories, Rockville, 
Maryland 

Dr. Yuet Wai Kan, School of Medicine, University of 
California, San Francisco 

Dr. Leon Kass, Henry R. Luce Professor of the Liberal 
Arts of Human Biology, University of Chicago 

Sheldon Krimsky, Ph.D., Department of Urban and 
Environmental Policy, Tufts University 

Eleanor Nightingale, Ph.D., Institute of Medicine, National 
Academy of Sciences 

Christine Oliver, Ph.D., Oil, Chemical and Atomic Workers 
International Union, Watertown, Massachusetts 

Richard Roblin, Ph.D., Cancer Biology Program, Frederick 
Cancer Research Center, Frederick, Maryland 

Frank Ruddle, Ph.D., Chairman, Department of Biology, 
Yale University 

Michael Shapiro, M.A., J.D., Law Center, University of 
Southern California 

Margery Shaw, M.D., J.D., Professor of Medical Genetics, 
Graduate School of Biomedical Sciences, University of 
Texas 

Maxine Singer, Ph.D., Chief, Laboratory of Biochemistry, 
National Cancer Institute, National Institutes of Health 

Marc Skolnick, Ph.D., College of Medicine, University of 
Utah 

Stephen Stitch, Ph.D., Professor of Philosophy, University 
of Maryland 

Leroy Walters, Ph.D., Director, Kennedy Institute for 
Bioethics, Georgetown University 

Additional Advisors from Federal Agencies (1981) 

Dr. French Anderson, Chief, Laboratory of Molecular 
Hematology, National Heart, Lung, and Blood Institute, 
National Institutes of Health 

John Fletcher, Ph.D., Assistant for Bioethics to the Director, 
Warren G. Magnuson Clinical Center, National Institutes 
of Health 



110 



Splicing Life: Appendix D 



Dr. William Gartland, Director, Office of Recombinant 
DNA Activities, National Institutes of Health 

Gretchen Kolsrud, Ph.D., Program Manager, Genetics and 
Population Program, Office of Technology Assessment, 
U.S. Congress 

Arthur Norberg, Ph.D., Program Manager, Ethics and 
Values in Science and Technology, National Science 
Foundation 

Dr. Joseph Schulman, Ph.D., Head, Human Biochemical and 
Developmental Genetics Section, National Institute of 
Child Health and Human Development, National 
Institutes of Health 

Dr. Bernard Talbot, Executive Secretary, Industrial 
Practices Subcommittee, National Institutes of Health 

Theological Consultants 

Representatives of Religious Organizations 

John R. Connery, S.J., for the U.S. Catholic Conference 

J. Robert Nelson, Ph.D., for the National Council of 
Churches 

Seymour Siegel, D.H.L., for the Synagogue Council of 
America 

Commentators 

Robert A. Brungs, S.J., Director, Institute for Theological 
Encounter with Science and Technology, St. Louis, 
Missouri 

James F. Childress, Ph.D., Professor of Religious Studies, 
University of Virginia 

Charles E. Curran, S.T.D., Professor of Moral Theology, 
Department of Theology, School of Religious Studies, 
Catholic University 

Sister Margaret A. Farley, Associate Professor of Ethics, 
Yale Divinity School 

James M. Gustafson, Ph.D., Professor of Theological Ethics, 
Divinity School, University of Chicago 

Karen Lebacqz, Ph.D., Associate Professor of Christian 
Ethics, Pacific School of Religion, Berkeley, California 

The Rev. Donald G. McCarthy, Ph.D., Director of 
Education, Pope John XXIII Medical-Moral Research and 
Education Center, St. Louis, Missouri 

J. Robert Nelson, Ph.D., Professor of Theology, Boston 
University 



Ill 



Rev. Kevin O'Rourke, O.P., J.C.D., S.T.L., Director, Center 
for Health Care Ethics, St. Louis University Medical 
Center 

Paul Ramsey, Ph.D., Professor of Religion, Princeton 
University 

Rev. Richard J. Roche, O.M.I., Ph.D., Saint Ann Church, 
Fayetteville, North Carolina 

Harmon L. Smith, Ph.D., Professor of Moral Theology and 
of Community and Family Medicine, Duke University 

Gabriel Vahanian, Ph.D., Professor of Religion, Syracuse 
University 



Index 



academia, commercial involve- 
ment with, 74 
amino acids, 28 

argininemia, gene therapy and, 
44 

Asilomar conference, 11 

benefits of gene splicing, 2, 36- 
38,42 

beta-thalassemia, gene therapy 
and, 43, 44 

Cambridge hearings on bioha- 

zards, 14, 16 
cancer, diagnosis and treatment 

of, 38 

cells, structure and function of, 
26-28 

cell fusion, genetic exchange 
and, 35 

chromosomes, structure and 
function of, 26-29 

clone, defined, 33 

cloning 
defined, 9-10 
of a gene, 33 

conjugation, genetic, 31 

consequences of gene splicing, 
see also psychological impact 
of gene splicing and societal 
impact of gene splicing 
for academia, 74 
commercialization and, 74-77 
cost-benefit distribution and, 
67 

evolutionary, 62-64 
genetic counseling and, 64 
human nature and, 14, 17, 69- 
71 

medical, 60-62 
personal identity and, 2, 68 
public concern about, 2, 13-17, 
71 

Cambridge hearings and, 
14-16 

Frankenstein story and, 2, 
14-16 

scientists' concern about, 14- 
15 

socially unacceptable, 71-73 
societal obligations and, 66 



control of gene splicing, 15, 73- 
74 

see also regulation 
corporations, academic rela- 
tions with, 74 

deoxyribonucleic acid, see DNA 
diagnosis of genetic disorders, 
3, 38-41 

DNA (deoxyribonucleic acid) 
early study of, 26 
genetic disorders and, 42-48 
history of research on, 9 
replication of, 29 
accidents during, 29 
genetic exchange and, 30 
restriction enzymes and, 32 
structure and function of, 27- 
28 

drugs produced by gene splic- 
ing, 2, 36-37, 61 

education of public, 20-21 
enzymes, restriction, 32-33 
diagnosis of genetic disorders 
and, 39 

equity, concerns about raised 
by gene splicing, 67-68 

evolution, ethical consider- 
ations and, 62-64 

Frankenstein story 
ethics of gene splicing and, 58 
public fears and, 14-16 

genes, structure and function of, 
26 

gene splicing 
defined, 8-10 
ethics of, 61 

genetic disorders treated by, 

see gene therapy 
history of, 8-9 

medical products from, 36-38 
naturally occurring forms of, 
30-31 

recombinant DNA techniques 

of, 30-35 
techniques of, 30-36 
unacceptable uses of, 57-60, 
71-73 
gene surgery, 42 
gene therapy 



114 



Splicing Life 



beta-thalassemia treated by, 
43, 44 

concerns about, 43, 47-48 
defined, 42 
experiments in, 43-45 
inheritable changes caused 

by, 46, 61 
popular notions of, 45 
genetic engineering, see gene 
splicing 

Genetic Engineering Commis- 
sion (GEC), 87-88 

genetic exchange, mechanisms 
of, 30-31 

genetic screening, 2-3, 38-41 
effect on occurrence of genes, 
8 

ethics and, 3, 41 
restriction enzymes and, 39 
genetics, early history of study 
of, 25 

germ cells, see also somatic 
cells 

composition of, 26 
gene therapy and, 45-48 
impact of alterations of, 3, 47- 
48 

likelihood of inheritable 
changes in, 46, 61 

heterozygote advantage, 63 
hormones, genetically engi- 
neered, 36 
human nature, genetic manipu- 
lation of, 68 

ethical considerations of, 2, 
14, 68-71 
hybridoma, 35 

hybrids, cross-species, ethical 
considerations of, 56-60 

inheritable changes in genes, 

see germ cells 
in vitro fertilization (IVF) 

defined, 9 

possible use with gene thera- 
py, 46 

insulin, genetically engineered, 
36 

Interagency Committee on Re- 
combinant DNA Research, 1, 
81, 85-86 

interferon, genetically engi- 
neered, 36-37 



legislation, regulation of gene 
splicing by, 12 

medical products, from gene 

splicing, 36-37 
medicine, genetic alterations as 

by-product of, 8 
Mendel, Gregor, 25 
monoclonal antibodies, 35, 38 
mutations of genes, 29-30, 39-41 

National Institutes of Health 
(NIH), see also Recombinant 
DNA Advisory Committee 
regulation of gene splicing 
and, 11 

natural law, ethics of gene splic- 
ing and, 55 

oligonucleotide hybridization, 
41 

oversight of gene splicing is- 
sues, 4-5 

evaluating need for, 23, 79 
objectives of, 82-84 

Pajaro Dunes conference, 75-76 

parents, rights and responsibili- 
ties of, 64-65 

plasmids, recombinant DNA 
and, 32-33 

"playing God," concerns about, 
3, 53-60 

see also religious views on 
gene splicing 
President's Commission 

focus and objectives of, 18-23 

as means of continuing over- 
sight, 87-88 

survey of government agen- 
cies, 18, 97-106 
psychological impact of gene 

splicing 

attitude toward family and 

children, 65 
sense of personal identity, 2, 

17, 62, 68 
public policy, gene splicing and, 
20 

education and, 20 
identification of issues of, 22 

recombinant DNA, 9, 30 

see also gene splicing 
Recombinant DNA Advisory 

Committee (RAC), 4, 11-12 

revision of, 4, 84-87 



Index 



115 



regulation of gene splicing 
churches' concern over lack 

of, 1, 7-8, 95-96 
governmental, 1, 11-13, 61, 84- 

88 

history of, 10-13 
by new oversight group, 2, 4-5, 
82-84 

by public agencies, 4, 44-45 
by scientists, 10-11 
religious views on gene splicing, 
53-60 

Biblical religions and, 53 

natural law and, 55 

new life forms and, 56 

objections raised by, 54 

species lines and, 58 
reproduction, human, ethics of 

gene splicing and, 64 
restriction enzymes, 32-33 

diagnosis of genetic disorders 
and, 39-41 
ribonucleic acid (RNA), 29 
risks of gene splicing 

safety mesures against, 3-4 

scientific concern about, 10, 
11, 15-16 



Harvard DNA laboratory 
and, 14 

Recombinant DNA Adviso- 
ry Committee and, 11-12 

scientific understanding of 
genes 

consequences of, 26, 54 
recent advances in, 2, 9, 17, 25 
sickle-cell disease, 39, 43 
slogans, misuse of in gene splic- 
ing, 21 

societal impact of gene splicing, 
13-17, 49, 72-73 

societal obligations, reproduc- 
tion and, 66 

somatic cells, 26, 42-45 
see also germ cells 

species barriers, 15, 30-32, 56-63 

transduction, genetic, 30 
transformation, genetic, 31 

uncertainty associated with 
gene splicing, 22, 60-61, 71 

vaccines, genetically engi- 
neered, 37 

zygote therapy, 46-47 



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